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1.
Braz. j. otorhinolaryngol. (Impr.) ; 87(6): 718-722, Nov.-Dec. 2021. tab, graf
Article in English | LILACS | ID: biblio-1350340

ABSTRACT

Abstract Introduction: Non-syndromic cleft lip with or without cleft palate is a common worldwide birth defect due to a combination of environmental and genetic factors. Genome-wide association studies reported the rs7078160 of Vax1 is closely related to non-syndromic cleft lip with or without cleft palate in European populations. The following studies showed the same results in Mongolian, Japanese, Filipino, Vietnamese populations etc. However, conflicting research had been reported in Chinese population, Objective: The aim of this study was to investigate the association between the rs7078160 polymorphism and non-syndromic cleft lip with or without cleft palate in Southern Chinese patients. Methods: In this study, we investigated the polymorphism distribution of rs7078160 in 100 complete patient trios (39 patients with non-syndromic cleft lip and palate; 36 patients with non-syndromic cleft lip only; 25 had non-syndromic cleft palate only; and their parents) from Southern ethnic Han Chinese. 60 healthy trios were selected as control. Polymerase chain reaction and Sanger sequencing were used to genotype rs7078160 in Vax1; both case-control and family-based associations were analyzed. Results: The case-control analyses revealed the rs7078160 polymorphism was significant, associated with non-syndromic cleft lip with or without cleft palate (p = 0.04) and non-syndromic cleft lip and palate (p = 0.01), but not associated with non-syndromic cleft lip only and nonsyndromic cleft palate only patients. The genotype composition of rs7078160 comprises mutated homozygous AA, heterozygous AG and wild homozygous GG. Cases with AG + AA genotypes compared with GG homozygotes showed an increased risk of non-syndromic cleft lip with or without cleft palate (p = 0.04, OR = 2.05, 95% CI: 1.01-4.16) and non-syndromic cleft lip and palate (p = 0.01, OR = 3.94, 95% CI: 1.34-11.54). In addition, we did not detect any transmissiondisequilibrium in rs7078160 (p = 0.68). Conclusion: This study suggests that rs7078160 polymorphism is a risk factor of non-syndromic cleft lip with or without cleft palate, and Vax1 is strongly associated with non-syndromic cleft lip with or without cleft palate in Southern Chinese Han populations.


Resumo Introdução: A fenda labial não sindrômica, com ou sem fenda palatina, é um defeito congênito comum em todo o mundo, devido a uma combinação de fatores ambientais e genéticos. O genome-wide association studies relatou que o polimorfismo rs7078160 do Vax1 está intimamente relacionado à fenda labial não sindrômica, com ou sem fenda palatina em populações europeias. Estudos subsequentes mostraram os mesmos resultados nas populações mongol, japonesa, filipina e vietnamita etc. No entanto, pesquisas conflitantes foram relatadas na população chinesa. Objetivo: Investigar a associação entre o polimorfismo rs7078160 e fenda labial não sindrômica, com ou sem fenda palatina, em pacientes do sul da China. Método: Tentamos investigar a distribuição do polimorfismo rs7078160 em 100 trios completos de pacientes (39 pacientes com fenda labial e palatina não sindrômica; 36 pacientes com fenda labial somente, não sindrômica; 25 com fenda palatina somente, não sindrômica e seus pais), da etnia Han do sul da China, e em 60 trios saudáveis selecionados como controle. Reação de polimerase em cadeia e o sequenciamento de Sanger foram uszados para genotipar o polimorfismo rs7078160 do Vax1 e tanto os casos-controle quanto as associações baseadas na família foram analisadas. Resultados: As análises de caso-controle revelaram que o polimorfismo rs7078160 estava significativamente associado a fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04) e fenda labial e palatina não sindrômica (p = 0,01), mas não estava associado a pacientes com fenda labial somente não sindrômica e fenda palatina somente não sindrômica. A composição do genótipo de rs7078160 compreende AA homozigoto mutado, AG heterozigoto e GG homozigoto selvagem. Casos com genótipos AG + AA comparados com GG homozigotos mostraram um risco aumentado de fenda labial não sindrômica, com ou sem fenda palatina (p = 0,04, OR = 2,05, IC de 95%: 1,01 ± 4,16) e fenda labial e palatina não sindrômica (p = 0,01, OR = 3,94, IC 95%: 1,34-11,54). Além disso, não detectamos desequilíbrio de transmissão em rs7078160 (p = 0,68). Conclusão: Este estudo sugere que o polimorfismo rs7078160 foi um fator de risco para fenda labial não sindrômica, com ou sem fenda palatina, e o gene Vax1 está fortemente associado com fenda labial não sindrômica, com ou sem fenda palatina em populações da etnia Han do sul da China.


Subject(s)
Humans , Cleft Lip/genetics , Cleft Palate/genetics , Transcription Factors/genetics , Case-Control Studies , China , Homeodomain Proteins/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Genome-Wide Association Study , Genotype
2.
J. pediatr. (Rio J.) ; 97(3): 321-328, May-June 2021. tab
Article in English | LILACS | ID: biblio-1279326

ABSTRACT

Abstract Objective This article presents a clinical and cytogenomic approach that focuses on the diagnosis of syndromic oral clefts (OCs). Methods The inclusion criteria were individuals with OC presenting four or more minor signs and no major defects (non-syndromic oral clefts [NSOCs]) as well as individuals with OC presenting at least another major defect, regardless of the number of minor signs (syndromic oral clefts [SOCs]). The exclusion criteria included NSOC with less than four minor signs, SOC with known etiology, as well as atypical oral clefts. Results Of 1647 individuals with OC recorded in the Brazilian Database of Craniofacial Anomalies, 100 individuals were selected for chromosome microarray analysis (CMA). Among these, 44 individuals were clinically classified as NSOC and 56 as SOC. CMA was performed for both groups, and abnormal CMA was identified in 9%, all previously classified as SCO. The clinical and CMA data analyses showed a significant predominance of abnormal CMA in individuals classified as SOC (p = 0.0044); prematurity, weight, length, and head circumference at birth were significantly lower in the group with abnormal CMA. Besides, minor signs were significantly higher in this group (p = 0.0090). Conclusion The rigorous selection of cases indicates that the significant variables could help in early recognition of SOC. This study reinforces the importance of applying the CMA technique to establish the diagnosis of SOC. This is an important and universal issue in clinical practice for intervention, care, and genetic counseling.


Subject(s)
Humans , Cleft Lip/genetics , Cleft Palate/genetics , Brazil , Chromosome Aberrations , Genomics
3.
Article in Chinese | WPRIM | ID: wpr-888366

ABSTRACT

OBJECTIVE@#To explore the genetic etiology for a fetus with congenital orofacial cleft.@*METHODS@#Single nucleotide polymorphism microarray (SNP array) was carried out on skin tissues sampled from the fetus following induced abortion for the detection of copy number variation (CNVs). Pathogenicity of the candidate gene was validated through experiment.@*RESULTS@#SNP array revealed that the fetus has carried a hemizygous 9.23Mb deletion at Xq21.31-q22.1(91 063 807-100 293 555), which was inherited from its mother. The region contained 13 OMIM genes and 1 ncRNA coding gene(MIR548M). Inhibiting of the expression of the MIR548M gene in oral epithelial celllines has resulted in up-regulation of the expression of SUMO1 gene which was known to involve in the pathogenesis of orofacial cleft.@*CONCLUSION@#Dosage insufficiency of the MIR548M gene may underlie the etiology of orofacial cleft in this fetus.


Subject(s)
Cleft Lip/genetics , Cleft Palate/genetics , DNA Copy Number Variations/genetics , Female , Fetus , Humans , MicroRNAs/genetics , Polymorphism, Single Nucleotide , Pregnancy , SUMO-1 Protein
4.
Article in Chinese | WPRIM | ID: wpr-879521

ABSTRACT

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with non-syndromic cleft lip and cleft palate (NSCLP).@*METHODS@#With informed consent obtained, members of the pedigree were subjected to clinical examination and history taking to exclude syndromic cleft lip and palate. One affected member was subjected to whole-exome sequencing and bioinformatics analysis. Candidate variant was verified by Sanger sequencing and co-segregation analysis of her family members and 100 unrelated healthy individuals.@*RESULTS@#Whole-exome sequencing and co-segregation analysis showed that all affected members of this pedigree have carried a heterozygous missense c.253A>G (p.Cys85Arg) variant in exon 4 of the IRF6 gene, which has co-segregated with the phenotype and was not found among the 100 unrelated healthy individuals.@*CONCLUSION@#The missense c.253A>G variant in exon 4 of the IRF6 gene probably underlay the NSCLP in this pedigree.


Subject(s)
Brain/abnormalities , China , Cleft Lip/genetics , Cleft Palate/genetics , Female , Humans , Interferon Regulatory Factors/genetics , Mutation, Missense , Pedigree , Whole Exome Sequencing
5.
Braz. j. otorhinolaryngol. (Impr.) ; 86(6): 696-702, Nov.-Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1142599

ABSTRACT

Abstract Introduction: Non-syndromic orofacial clefts have a complex etiology due to the contribution from both genetic and environmental risk factors, as well as the interaction between them. Among the more than 15 susceptibility loci for non-syndromic orofacial clefts with considerable statistical and biological support, the IRF6 is the most validated gene by the majority of studies. Nonetheless, in genetically heterogeneous populations such as Brazilian, the confirmation of association between non-syndromic orofacial clefts and IRF6 common variants is not a consolidated fact and unrecognized IRF6 variants are poorly investigated. Objective: The aim of this study was to investigate the association of IRF6 polymorphisms with non-syndromic orofacial clefts development in a population from northeast Brazil. Methods: Blood samples of 186 non-syndromic orofacial clefts patients and 182 controls from Rio Grande do Norte, Brazil, were obtained to analyze IRF6 polymorphisms (rs2235371, rs642961, rs2236907, rs861019, and rs1044516) by real-time polymerase chain reaction. Non-syndromic orofacial clefts patients were classified in cleft lip and palate, cleft palate only and cleft lip only groups. Results: The genotype and allele frequencies of single nucleotide polymorphism rs2235371 in IRF6 showed significant differences in patients with cleft palate when compared to the controls, whereas no association was shown between rs642961, rs2236907, rs861019, and rs1044516 and non-syndromic orofacial clefts. Conclusion: The association found between rs2235371 and isolated cleft palate should be interpreted with caution due to the low number of individuals investigated, and more studies with larger sample size are needed to confirm these association. In addition, there is a lack of association of the rs642961, rs2236907 and rs861019 polymorphisms with non-syndromic orofacial clefts susceptibility.


Resumo Introdução: As fendas orofaciais não sindrômicas possuem uma etiologia complexa devido à contribuição de fatores de risco genéticos e ambientais, assim como a interação entre eles. Dentre os mais de 15loci de susceptibilidade para as fendas orofaciais não sindrômicas com considerável suporte estatístico e biológico, o IRF6 é o gene mais validado pela maioria dos estudos. Apesar disso, em populações geneticamente heterogêneas como a brasileira, a confirmação da associação entre as fendas orofaciais não sindrômicas e as variantes mais comuns do IRF6 ainda não é um fato consolidado e outras variantes não tão conhecidas IRF6 são pouco investigadas. Objetivo: O objetivo deste estudo foi investigar a associação de variados polimorfismos do IRF6 com o desenvolvimento das fendas orofaciais não sindrômicas em uma população do nordeste do Brasil. Método: Amostras de sangue de 186 pacientes com fendas orofaciais não sindrômicas e 182 controles do estado do Rio Grande do Norte, Brasil, foram obtidas para analisar os polimorfismos do IRF6 (rs2235371, rs642961, rs2236907, rs861019 e rs1044516) por reação em cadeia da polimerase em tempo real. Os pacientes com fendas orofaciais não sindrômicas foram classificados em fenda labiopalatina, fenda palatina isolada e fenda labial isolada. Resultados: As frequências genotípica e alélica do polimorfismo de único nucleotídeo rs2235371 no IRF6 mostraram-se significativamente diferentes em pacientes com fenda palatina isolada quando comparadas às dos controles, enquanto que nenhuma associação foi encontrada entre rs642961, rs2236907, rs861019 e rs1044516 e risco para o desenvolvimento das fendas orofaciais não sindrômicas. Conclusão: A associação encontrada entre rs2235371 e fenda palatina isolada deve ser interpretada com cautela devido ao baixo número de indivíduos investigados, sendo necessários mais estudos com um tamanho amostral maior para confirmar essa associação. Além disso, não foram encontradas associações significativas entre os demais polimorfismos do IRF6 rs642961, rs2236907, rs861019 e rs1044516 e a susceptibilidade às fendas orofaciais não sindrômicas.


Subject(s)
Humans , Cleft Lip/genetics , Cleft Palate/genetics , Interferon Regulatory Factors/genetics , Polymorphism, Genetic , Brazil , Genetic Predisposition to Disease , Genotype
6.
Int. j. odontostomatol. (Print) ; 13(3): 345-349, set. 2019. graf
Article in English | LILACS | ID: biblio-1012434

ABSTRACT

ABSTRACT: A standardized photographic documentation is reproducible, which facilitates the evaluation of new techniques, treatment planning, and comparison of results. Clinical photography is important to impart scientific education to health professionals, because techniques can be better understood by the listener or reader when they are well illustrated. Documentation of consistent imaging of clinical diagnosis and treatment is also essential in medical-legal cases. Highquality clinical photographs along with radiographs and other medical and dental images should become an integral part of patients' medical records. Variables such as lens selection, camera position, distance, and patient's position should be understood and controlled by healthcare personnel for acquiring accurate photographs. In the case of patients with craniofacial deformities, such as cleft lip and palate, it is important to establish the standardization of photographic records because the patients' aesthetic evaluation is a fundamental clinical indicator in the deformity analysis, besides assisting the planning of patients' multidisciplinary treatment. This article aims to assist health professionals in acquiring standardized facial photographs (front, right profile, left profile, and submental oblique view) of patients with cleft lip and palate.


RESUMEN: Una documentación fotográfica estandarizada es reproducible, lo que facilita la evaluación de nuevas técnicas, la planificación del tratamiento y la comparación de resultados. La fotografía clínica es importante para impartir educación científica a los profesionales de la salud, ya que el oyente o lector puede comprender mejor las técnicas cuando están bien ilustradas. La documentación de imágenes consistentes de diagnóstico clínico y tratamiento también es esencial en casos médico-legales. Las fotografías clínicas de alta calidad junto con las radiografías y otras imágenes médicas y dentales deben convertirse en una parte integral de los registros médicos de los pacientes. El personal de atención médica debe comprender y controlar las variables como la selección de la lente, la posición de la cámara, la distancia y la posición del paciente para obtener fotografías precisas. En el caso de pacientes con deformidades craneofaciales, como labio leporino y paladar hendido, es importante establecer la estandarización de los registros fotográficos porque la evaluación estética de los pacientes es un indicador clínico fundamental en el análisis de la deformidad, además de ayudar en la planificación del tratamiento multidisciplinario del paciente. Este artículo pretende ayudar a los profesionales de la salud a adquirir fotografías faciales estandarizadas (frente, perfil derecho, perfil izquierdo y vista oblicua submental) de pacientes con labio leporino y paladar hendido.


Subject(s)
Humans , Cleft Lip/genetics , Cleft Lip/pathology , Cleft Palate/genetics , Cleft Palate/pathology , Image Processing, Computer-Assisted , Brazil , Photography, Dental/methods , Photography, Dental/standards , Informed Consent
7.
Rev. bras. cir. plást ; 34(1): 94-100, jan.-mar. 2019. ilus, tab
Article in English, Portuguese | LILACS | ID: biblio-994554

ABSTRACT

Introdução: As fissuras labiopalatinas são as malformações congênitas mais comuns dentre as que ocorrem na cabeça e pescoço, e se devem à falha de fusão dos processos faciais embrionários durante as primeiras 12 semanas de gestação. Sua apresentação fenotípica é variada e com diferentes níveis de complexidade. O objetivo é determinar o perfil epidemiológico dos pacientes portadores de fissuras labiopalatinas atendidos no Hospital Regional da Asa Norte (HRAN) quanto a sexo, tipo de fissura, lateralidade, idade, presença de síndromes associadas e procedimentos cirúrgicos corretivos. Métodos: Trata-se de um estudo descritivo retrospectivo no qual foram analisados 322 prontuários de pacientes atendidos pela equipe do HRAN no período de agosto de 2013 a julho de 2017. Os dados colhidos foram lançados em planilha Excel e submetidos à análise estatística. O trabalho foi aprovado pelo Comitê de Ética e Pesquisa. Resultados: Dos 322 pacientes atendidos no serviço, 169 eram do sexo masculino (52,48%). O tipo de fissura mais frequente foi a transforâmica (65,25%). Com relação à lateralidade, observou-se maior predomínio da fissura à esquerda (20,50%). Apenas 19% dos pacientes possuem malformações associadas. A queiloplastia foi a correção cirúrgica mais realizada pelo serviço (54%). A idade dos pacientes variou de 1 ano até 53 anos, com mediana de 1,87 anos. Conclusão: O estudo contribuiu com informações importantes para a sociedade, governo e profissionais envolvidos no tratamento. Em consonância com a literatura, observou-se que a fissura mais prevalente foi a transforâmica unilateral esquerda e a cirurgia mais realizada foi a queiloplastia.


Introduction: Cleft lip and palate, the most common congenital malformations of the head and neck, result from fusion failure of embryonic facial processes during the first 12 weeks of pregnancy. Their phenotypic presentation varies and involves different levels of complexity. The objective is to determine the epidemiological profile of patients with cleft lip and palate treated at the Hospital Regional da Asa Norte regarding sex, cleft type, laterality, age, presence of associated syndromes, and corrective surgical procedures. Methods: This was a retrospective descriptive study of 322 medical records of patients treated by the HRAN team from August 2013 to July 2017. The data collected were entered into an Excel spreadsheet and submitted to statistical analysis. The study received ethical approval. Results: Of the 322 patients enrolled in the service, 169 were male (52.48%). The most frequent type of cleft was the trans-foramen (65.25%). With regard to laterality, a higher prevalence of cleft was observed on the left (20.50%). Only 19% of the patients had associated malformations. Cheiloplasty was the most frequent surgical correction performed by service (54%). The age of the patients was 1­53 years (median, 1.87 years). Conclusion: The study contributes information important to society, government, and treatment professionals. In line with the literature, the more prevalent cleft was unilateral left trans-foramen and the most frequent surgery was cheiloplasty.


Subject(s)
Humans , Male , Female , Middle Aged , Patients/statistics & numerical data , Congenital Abnormalities , Dental Fissures/congenital , Cleft Lip , Cleft Palate/surgery , Cleft Palate/complications , Cleft Palate/genetics , Reconstructive Surgical Procedures/methods
8.
J. appl. oral sci ; 27: e20180649, 2019. graf
Article in English | LILACS, BBO | ID: biblio-1040227

ABSTRACT

Abstract Objective: Cleft palate (CP) is a congenital birth defect caused by the failure of palatal fusion. Little is known about the potential role of DNA methylation in the pathogenesis of CP. This study aimed to explore the potential role of DNA methylation in the mechanism of CP. Methodology: We established an all-trans retinoic acid (ATRA)-induced CP model in C57BL/6J mice and used methylation-dependent restriction enzymes (MethylRAD, FspEI) combined with high-throughput sequencing (HiSeq X Ten) to compare genome-wide DNA methylation profiles of embryonic mouse palatal tissues, between embryos from ATRA-treated vs. untreated mice, at embryonic gestation day 14.5 (E14.5) (n=3 per group). To confirm differentially methylated levels of susceptible genes, real-time quantitative PCR (qPCR) was used to correlate expression of differentially methylated genes related to CP. Results: We identified 196 differentially methylated genes, including 17,298 differentially methylated CCGG sites between ATRA-treated vs. untreated embryonic mouse palatal tissues (P<0.05, log2FC>1). The CP-related genes Fgf16 (P=0.008, log2FC=1.13) and Tbx22 (P=0.011, log2FC=1.64,) were hypermethylated. Analysis of Fgf16 and Tbx22, using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), identified 3 GO terms and 1 KEGG pathway functionally related to palatal fusion. The qPCR showed that changes in expression level negatively correlated with methylation levels. Conclusions: Taken together, these results suggest that hypermethylation of Fgf16 and Tbx22 is associated with decreased gene expression, which might be responsible for developmental failure of palatal fusion, eventually resulting in the formation of CP.


Subject(s)
Animals , Male , Female , Cleft Palate/genetics , DNA Methylation , T-Box Domain Proteins/genetics , Fibroblast Growth Factors/genetics , Reference Values , Gene Expression , Cleft Palate/embryology , Cleft Palate/pathology , Sequence Analysis, DNA , T-Box Domain Proteins/analysis , Protein Interaction Domains and Motifs , Real-Time Polymerase Chain Reaction , Fibroblast Growth Factors/analysis , Mice, Inbred C57BL
9.
Braz. j. otorhinolaryngol. (Impr.) ; 84(4): 473-477, July-Aug. 2018. tab
Article in English | LILACS | ID: biblio-951849

ABSTRACT

Abstract Introduction Transcription factors are very diverse family of proteins involved in activating or repressing the transcription of a gene at a given time. Several studies using animal models demonstrated the role of transcription factor genes in craniofacial development. Objective We aimed to investigate the association of IRF6 intron-6 polymorphism in the non-syndromic cleft lip with or without palate in a South Indian population. Methods 173 unrelated nonsyndromic cleft lip with or without cleft palate patients and 176 controls without clefts patients were genotyped for IRF6 rs2235375 variant by allele-specific amplification using the KASPar single nucleotide polymorphism genotyping system. The association between interferon regulatory factor-6 gene intron-6 dbSNP208032210:g.G>C (rs2235375) single nucleotide polymorphism and non-syndromic cleft lip with or without palate risk was investigated by chi-square test. Results There were significant differences in genotype or allele frequencies of rs2235375 single nucleotide polymorphism between controls and cases with non-syndromic cleft lip with or without palate. IRF6 rs2235375 variant was significantly associated with increased risk of non-syndromic cleft lip with or without palate in co-dominant, dominant (OR: 1.19; 95% CI 1.03-2.51; p = 0.034) and allelic models (OR: 1.40; 95% CI 1.04-1.90; p = 0.028). When subset analysis was applied significantly increased risk was observed in cleft palate only group (OR dominant: 4.33; 95% CI 1.44-12.97; p = 0.005). Conclusion These results suggest that IRF6 rs2235375 SNP play a major role in the pathogenesis and risk of developing non-syndromic cleft lip with or without palate.


Resumo Introdução Fatores de transcrição constituem uma família de proteínas muito diversa envolvida na ativação ou repressão da transcrição de um gene, em um determinado momento. Vários estudos usando modelos animais demonstraram o papel dos genes do fator de transcrição no desenvolvimento craniofacial. Objetivo Nosso objetivo foi investigar a associação do polimorfismo IRF6 intron-6 na fenda labial não sindrômica com ou sem fenda palatina em uma população do sul da Índia. Método Um total de 173 pacientes com fenda labial não sindrômica com ou sem fenda palatina e 176 controles sem fendas foram genotipados para a variante IRF6 rs2235375 por amplificação alelo-específica utilizando o sistema KASPar de genotipagem de polimorfismo de nucleotídeo único. A associação entre o polimorfismo de nucleotídeo único Fator 6 Regulatório do Interferon (IRF6) intron-6 dbSNP208032210:g.G>C (rs2235375) e o risco de fenda labial não sindrômica com ou sem fenda palatina foi investigado pelo teste qui-quadrado. Resultados Houve diferenças significativas nas frequências de genótipos ou alelos do rs2235375 SNP entre controles e casos com fenda labial não sindrômica com ou sem fenda palatina. A variante IRF6 rs2235375 foi significativamente associada ao aumento do risco de fenda labial não sindrômica com ou sem fenda palatina em modelos codominantes, dominantes (OR: 1,19; IC 95%: 1,03-2,51; p = 0,034) e alélicos (OR: 1,40; IC 95%: 1,04-1,90; p = 0,028). Quando a análise do subgrupo foi realizada, um risco significativamente aumentado foi observado no grupo Fenda Palatina Isolada (OR dominante: 4,33; IC 95%: 1,44-12,97; p = 0,005). Conclusões Esses resultados sugerem que o polimorfismo de nucleotídeo único IRF6 rs2235375 desempenha um papel importante na patogênese e no risco de desenvolvimento de fenda labial não sindrômica com ou sem fenda palatina.


Subject(s)
Humans , Male , Female , Cleft Lip/genetics , Cleft Palate/genetics , Polymorphism, Single Nucleotide/genetics , Interferon Regulatory Factors/genetics , Case-Control Studies , Risk Factors , Cleft Lip/ethnology , Cleft Palate/ethnology , Genetic Association Studies , Genotyping Techniques , Gene Frequency , India
11.
J. appl. oral sci ; 25(6): 650-656, Nov.-Dec. 2017. tab, graf
Article in English | LILACS, BBO | ID: biblio-893673

ABSTRACT

Abstract Non-syndromic cleft lip with or without palate (NSCL/P) is a common congenital malformation worldwide, with complex etiology. It has been proposed that interaction of genes and environmental factors play a role in the predisposition to this disease. Objectives: The aim of this study was to examine the association between AXIN2 (axis inhibition protein 2) rs7224837, BMP4 (bone morphogenetic protein 4) rs17563, and IRF6 (interferon regulatory factor 6) rs861019 and 2235371 polymorphisms and NSCL/P in an Iranian population. Material and Methods: This case-control study was carried out on 132 unrelated NSCL/P patients and 156 healthy subjects. The variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The findings suggest that BMP4 rs17563 polymorphism significantly decreased the risk of NSCL/P in codominant (OR=0.36, 95%CI=0.17-0.79, p=0.012, CT vs CC and OR=0.11, 95%CI=0.01-0.88, p = 0.019, TT vs CC), dominant (OR=0.30, 95%CI=0.15-0.62, p = 0.0007, CT+TT vs CC), recessive (OR=0.12, 95%CI=0.02-0.99, p = 0.023, TT vs CC+CT), overdominant (OR=0.39, 95%CI = 0.18-0.84, p=0.021, CT vs CC+TT), and allele (OR=0.28, 95%CI=0.15-0.55, p<0.0001, T vs C) inheritance models. Our findings did not support an association between AXIN2 rs7224837 and IRF6 rs861019 polymorphism and risk/protection of NSCL/P. The IRF6 2235371 variant was not polymorphic in our population. Conclusion: The results indicate that the BMP4 rs17563 variant is likely to confer a protective effect against the occurrence of NSCL/P in a sample of the southeast Iranian population.


Subject(s)
Humans , Male , Female , Child , Cleft Lip/genetics , Cleft Palate/genetics , Interferon Regulatory Factors/genetics , Bone Morphogenetic Protein 4/genetics , Axin Protein/genetics , Polymorphism, Restriction Fragment Length , Case-Control Studies , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Gene Frequency , Genotype , Iran
12.
Rev. paul. pediatr ; 35(2): 234-238, abr.-jun. 2017. tab, graf
Article in Portuguese | LILACS | ID: biblio-902837

ABSTRACT

RESUMO Objetivo: EEC é um acrônimo para uma síndrome autossômica dominante caracterizada clinicamente por ectrodactilia (E), displasia ectodérmica efissura labiopalatal (C). Nosso objetivo foi relatar um caso raro de irmãos afetados pela síndrome de ectrodactilia, displasia ectodérmica efissura labiopalatal (EEC) com pais hígidos. Descrição do caso: O paciente era o terceiro filho de pais jovens e hígidos, os quais não apresentavam nenhuma anomalia menor ou maior de mãos e pés ou anomalias de pele, cabelos e dentes. O casal tinha história prévia de duas crianças com malformação de mãos e pés, similar à do paciente. O primeiro foi natimorto e o segundo, prematuro, falecendo nos primeiros dias de vida, pelas consequências da prematuridade. Após o nascimento, o paciente apresentou desconforto respiratório, com necessidade de intubação orotraqueal e ventilação mecânica. No exame físico, verificaram-se a presença de fissura labiopalatal e ectrodactilia de mãos e pés, com ausência do segundo e terceiro dedos em ambas as mãos e defeitos de redução acometendo principalmente o segundo dedo dos pés. A criança apresentou pneumotórax e parada cardiorrespiratória, morrendo com 1 mês e 26 dias de vida. Comentários: Descrevemos aqui um caso de irmãos com síndrome EEC, indicativo de mosaicismo germinativo. Na revisão da literatura, observaram-se apenas três relatos similares. Este caso reforça a possibilidade do mosaicismo germinativo ser um mecanismo de herança mais comum do que se acreditava previamente para casos da síndrome EEC.


ABSTRACT Objective: EEC is an acronym for an autosomal dominant syndrome clinically characterized by ectrodactyly (E), ectodermal dysplasia (E) and cleft lip/palate (C). Our aim was to describe a rare case of siblings affected by ectrodactyly, ectodermal dysplasia and cleft lip/palate (EEC) syndrome presenting normal parents. Case description: The patient was the third son of young and healthy parents. The parents did not present any minor or major anomaly of hands, feet or skin, hair and teeth. The couple had a previous history of two children with hands and feet malformations similar to the present patient. The first was a stillborn, and the second one a preterm infant that died in the first days after birth due to the consequences of prematurity. After birth, the patient presented respiratory distress with need of endotracheal intubation and mechanic ventilation. At physical examination, there were cleft lip/palate, hands and feet ectrodactyly, with absence of the second and third fingers in both hands, and reduction defects affecting mainly the second toes. The child presented pneumothorax and cardiorespiratory arrest and died at 1 month and 26 days. Comments: Herein we described a case of siblings with EEC syndrome, indicative of a germline mosaicism. In the literature review, there was the description of only three similar reports. The present case strengthens the possibility that germline mosaicism may be a more common inheritance mechanism than previously thought in cases of EEC syndrome.


Subject(s)
Humans , Male , Infant, Newborn , Ectodermal Dysplasia/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Mosaicism , Parents , Pedigree , Phenotype , Germ-Line Mutation , Fatal Outcome
13.
Int. j. odontostomatol. (Print) ; 10(1): 75-84, abr. 2016. ilus
Article in Spanish | LILACS | ID: lil-782625

ABSTRACT

El objetivo fue determinar la expresión génica del factor de crecimiento transformante beta (TGF-ß) y posibles factores de riesgo en niños con y sin fisuras labio palatina no sindrómicas (FLPNS). Diseño de casos (Niños con fisuras orales; n= 20) y controles (niños no afectados; n= 40). A partir de muestras de saliva se realizó la extracción de mRNA utilizando el RNeasy® Protect Saliva Mini Kit-QIAgen y la expresión génica del TGF-ß mediante la reacción en cadena de la polimerasa en transcriptasa reversa, además se aplicó un cuestionario para registrar características sociodemográficas y posibles factores de riesgo durante el periodo de concepción (medicamentos, enfermedades, alcohol, cigarrillo y edad de los padres).Los datos fueron analizados mediante medidas de tendencia central y dispersión, frecuencias y porcentajes, para establecer asociaciones se utilizaron las prueba T-Student, Chi-cuadrado y Odds ratio, asumiendo un límite de confianza de 0,05. El promedio de edad de los participantes fue de 6,8 (DE= 4,6) años y el 63,3 % eran de sexo masculino. Al evaluar los posibles factores asociados con el desarrollo de FLPNS no se encontraron diferencias significativas, sin embargo el 11,7 % de las madres habían ingerido algún tipo de medicamentos durante el embarazo, el 1,7 % habían fumado algún cigarrillo y el 13,3 % ingerido alcohol. Existieron diferencias significativas en la expresión génica del TGF-ß entre los grupos (p= 0,0205), siendo menor en grupo de casos. Los factores de riesgo evaluados mostraron poca evidencia de asociación con la presencia de FLAPNS, los niños con esta alteración tienen menor expresión génica del TGF-ß, sugiriendo que alteraciones moleculares en la vía de señalización del TGF-ß posiblemente están involucradas en el desarrollo de las fisuras labio palatinas, ya que se pueden afectar procesos de diferenciación, crecimiento y proliferación celular, en donde participan varios genes incluyendo el TGF-ß.


The aim of this study was to determine gene expression of transforming growth factor beta (TGF-ß) and possible risk factors in children with and without non-syndromic oral clefts. Cases (Children with cleft lip and palate; n= 20) and controls (unaffected children; n= 40) study, from saliva samples mRNA extraction was performed using the RNeasy® Protect Saliva Mini Kit-QIAgen and gene expression of TGF-ß by reverse transcriptase polymerase chain reaction, a questionnaire was also applied to record sociodemographic characteristics and possible risk factors. Data were analyzed using measures of central tendency and dispersion, frequencies and percentages. Odds ratio, Chi-square and T-Student tests were used to determine association (p<0.05). The average age of participants was 6.8 (SD= 4.6) years and 63.3 % were male. No statistically significant association was found between any of the possible risk factors examined with the development of oral clefts (p> 0.05), however it was reported that 11.7 % of mothers had ingested some type of drug during pregnancy, 1.7 % reported maternal smoking and 13.3 % reported alcohol consumption. There were significant differences in gene expression levels of TGF-ß between groups (p= 0.0205), being lower in children with oral clefts. Most environmental risk factors evaluated here gave little evidence of association with the presence of oral clefts. Children with oral clefts have lower gene expression of TGF-ß, suggesting that molecular alterations in the signaling pathway of TGF-ß are possibly involved in the development of cleft lip and palate, as they can affect processes of differentiation, growth and proliferation cell, where several genes are involved including TGF-ß.


Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Adolescent , Transforming Growth Factor beta/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Saliva/chemistry , Case-Control Studies , Gene Expression , Risk Factors , Reverse Transcriptase Polymerase Chain Reaction
14.
Braz. dent. j ; 26(6): 561-565, Nov.-Dec. 2015. tab
Article in English | LILACS | ID: lil-769552

ABSTRACT

The aim of this study was to evaluate the association of the polymorphisms in TCN2 (rs1801198) gene and in MTRR (rs1801394) gene with nonsyndromic cleft lip and/or palate (NSCL/P) in a Brazilian population. Genomic DNA was extracted from buccal cells. The polymorphisms in TCN2 (rs1801198) and MTRR (rs1801394) genes were genotyped by carrying out real-time PCR and Taqman assay. Chi-square test was used to determine the association between genotype and allele frequencies with NSCL/P and NSCL/P subgroups (cleft lip only, cleft lip and palate, and cleft palate only). Eight hundred and sixty seven unrelated individuals (401 cases with NSCL/P and 466 individuals without cleft) were evaluated. Genotype distributions of TCN2 and MTRR polymorphisms were in Hardy-Weinberg equilibrium. The TCN2 polymorphic genotype GG was identified in 16.7% of the NSCL/P group and in 14.1% of the non-cleft group (p>0.05). Similarly, the frequency of MTRR genotype (GG) was similar in NSCL/P group (15.5%) and control group (17.8%) (p>0.05). Multivariate analysis showed an association between MTRR and the subgroup that the mother smoked during pregnancy (p=0.039). Our findings did not demonstrate an association between TCN2 polymorphisms and NSCL/P, however suggests an association between MTRR and NSCL/P etiology.


Resumo O objetivo desse estudo foi avaliar a associação entre os polimorfismos no gene TCN2 (rs1801198) e no gene MTRR (rs1801394) com fissura de lábio e/ou palato não sindrômica (NSFL/P) em uma população brasileira. DNA genômico foi extraído de células bucais. Os polimorfismos nos genes TCN2 (rs1801198) e MTRR (rs1801394) foram genotipados através do PCR em tempo real pelo método Taqman. O teste do qui-quadrado foi utilizado para determinar a associação entre a frequência alélica e genotípica e NSFL/P e nos subtipos (fissura de lábio, fissura de lábio com palato e fissura de palato). Oitocentos e sessenta e sete indivíduos não aparentados (401 casos com NSFL/P e 466 indivíduos sem fissura) foram avaliados. A distribuição dos genótipos dos polimorfismos de TCN2 e MTRR estavam em equilíbrio de Hardy-Weinberg. O genótipo polimórfico GG do gene TCN2 foi identificado em 16,7% do grupo com NSFL/P e em 14,1% do grupo sem fissura (p>0,05). Da mesma forma, a freqüência do genótipo GG do gene MTRR foi bastante semelhante entre o grupo com NSFL/P (15,5%) e o grupo controle (17,8%). A análise multivariada mostrou associação entre o gene MTRR e o subgrupo que apresentou tabagismo materno durante a gestação (p=0,039). Nossos resultados mostraram que não há associação entre os polimorfismos nos genes TCN2 e NSFL/P, entretanto sugerem uma associação entre MTRR e a etiologia de NSFL/P.


Subject(s)
Humans , Male , Female , Child , Adolescent , Adult , Young Adult , Cleft Lip/genetics , Cleft Palate/genetics , Folic Acid/metabolism , Genetic Predisposition to Disease , Vitamin B 12/metabolism , Case-Control Studies , Polymorphism, Genetic
15.
J. appl. oral sci ; 23(4): 390-396, July-Aug. 2015. tab, ilus
Article in English | LILACS, BBO | ID: lil-759356

ABSTRACT

AbstractNonsyndromic oral clefts are considered a problem of public health in Brazil, presenting a multifactorial etiology that involves genetic and environmental components, such as maternal alcohol consumption. Several candidate genes have been investigated to identify some association with nonsyndromic clefts risk. The epidermal growth factor (EGF) gene is implicated in the normal craniofacial development and its functional +61 A>G polymorphism has been related to cancer susceptibility. It has been suggested that cancer and oral clefts may share the same molecular pathways.Objective Our goal was to evaluate the association between the EGF+61 A>G polymorphism and nonsyndromic oral clefts susceptibility.Material and Methods The case-control study included 218 cleft cases and 253 controls from Brazil. The control group was comprised of individuals without congenital malformations, dental anomalies and family history of clefts. The cleft phenotypes and subphenotypes were determined based on clinical examination. Genomic DNA was extracted from oral mucosa cells obtained by mouthwash. The EGF+61 A>G polymorphism genotype was determined by polymerase chain reaction-restriction fragment length polymorphism.Results We noticed the association between maternal alcohol consumption during pregnancy and cleft occurrence. The A allele and AA genotype were over-represented in cleft cases compared with control group when we considered the bilateral cleft lip with or without cleft palate (CL±P) cases, cleft cases with tooth agenesis and cleft cases presenting family history of cleft, but the differences were not statistically significant. Contradictorily, the G allele was higher in cleft palate only (CP) cases than in control group, showing a borderline p value. Comparing the different cleft phenotypes, we observed statistical differences between CP and CL±P cases. Our data suggest the EGF+61 A>G polymorphism was not related with nonsyndromic oral clefts susceptibility in a Brazilian population, but supported the different genetic background between CL±P and CP. Moreover, we confirmed the potential effect of maternal alcohol intake on cleft risk in our population.


Subject(s)
Humans , Male , Female , Pregnancy , Child , Adolescent , Adult , Young Adult , Cleft Lip/genetics , Cleft Palate/genetics , Epidermal Growth Factor/genetics , Genetic Association Studies , Polymorphism, Restriction Fragment Length , Alcohol Drinking/adverse effects , Brazil , Case-Control Studies , Gene Frequency , Genotype , Polymerase Chain Reaction , Risk Factors , Sex Factors , Smoking/adverse effects
16.
J. appl. oral sci ; 23(3): 272-278, May-Jun/2015. tab, graf
Article in English | LILACS, BBO | ID: lil-752426

ABSTRACT

Objective Nonsyndromic cleft lip with or without cleft palate (NS-CL/P) are among the most common congenital birth defects worldwide. Several lines of evidence point to the involvement of folate, as well as folate metabolizing enzymes in risk reduction of orofacial clefts. Dihydrofolate reductase (DHFR) enzyme participates in the metabolic cycle of folate and has a crucial role in DNA synthesis, a fundamental feature of gestation and development. A functional polymorphic 19-bp deletion within intron-1 of DHFR has been associated with the risk of common congenital malformations. The present study aimed to evaluate the possible association between DHFR 19-bp deletion polymorphism and susceptibility to NS-CL/P in an Iranian population. Material and Methods The current study recruited 100 NS-CL/P patients and 100 healthy controls. DHFR 19-bp deletion was determined using an allele specific-PCR method. Results We observed the DHFR 19-bp homozygous deletion genotype (D/D) vs. homozygous wild genotype (WW) was more frequent in controls than in NS-CL/P patients (25% vs. 13%), being associated with a reduced risk of NS-CL/P in both codominant (OR=0.33, P=0.027) and recessive (OR=0.45, P=0.046) tested inheritance models. We also stratified the cleft patients and reanalyzed the data. The association trend for CL+CL/P group compared to the controls revealed that the DD genotype in both codominant (OR=0.30, P=0.032) and recessive models (OR=0.35, P=0.031) was associated with a reduced risk of CL+CL/P. Conclusions Our results for the first time suggested the DHFR 19-bp D/D genotype may confer a reduced risk of NS-CL/P and might act as a protective factor against NS-CL/P in the Iranian subjects. .


Subject(s)
Humans , Male , Female , Infant , Child, Preschool , Child , Adolescent , Adult , Middle Aged , Young Adult , Brain/abnormalities , Cleft Lip/genetics , Cleft Palate/genetics , Gene Deletion , Polymorphism, Genetic/genetics , Tetrahydrofolate Dehydrogenase/genetics , Case-Control Studies , Gene Frequency , Genetic Association Studies , Logistic Models , Polymerase Chain Reaction , Reference Values , Risk Assessment
17.
Rev. méd. Chile ; 143(4): 444-450, abr. 2015. tab
Article in Spanish | LILACS | ID: lil-747550

ABSTRACT

Background: NAT genes are considered candidate genes for the genetic predisposition to non-syndromic Cleft lip with or without cleft palate (NSCLP), since they codify for N-acetyltransferases, enzymes responsible for the biotransformation of arylamines, hydrazine drugs, and a great number of toxins and carcinogens present in diet, cigarette smoke, and environment. Aim: To determine the association between alleles determining slow acetylator phenotype and the risk of NSCLP. Material and Methods: We analyzed *5 (481C>T), *6 (590G>A) and *7 (857G>A) alleles which determine the slow acetylator phenotype and *4 (wild type) allele by polymerase chain reaction/restriction fragment length polymorphism in 97 progenitor-case trios of NSCLP in Argentinian Obstetric Wards. We evaluated the transmission disequilibrium (TDT). Results: TDT showed a positive association between allele *5 and NSCLP (odds ratio = 1,6; p = 0,03). Conclusions: The presence of *5 allele is significantly higher in cases with congenital NSCLP.


Subject(s)
Female , Humans , Male , Arylamine N-Acetyltransferase/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Polymorphism, Restriction Fragment Length/genetics , Alleles , Amplified Fragment Length Polymorphism Analysis , Analysis of Variance , Argentina , Fathers , Genetic Predisposition to Disease , Genotype , Genetic Carrier Screening , Linkage Disequilibrium , Mothers
18.
Bauru; s.n; 2015. 108 p. ilus, tab, graf.
Thesis in Portuguese | LILACS, BBO | ID: biblio-867341

ABSTRACT

O propósito deste trabalho foi investigar a ocorrência de mutações e polimorfismos em genes candidatos aos defeitos na formação do esmalte dentário em indivíduos com fissura labiopalatina (FLP) transforame incisivo unilateral ou bilateral isolada e associar o genótipo-fenótipo dos indivíduos com FLP e malformação dentária (MD) nos dentes incisivos centrais superiores permanentes. Foram coletadas amostras de saliva de 165 indivíduos de 6 a 15 anos de idade, de ambos os sexos, divididos em 4 grupos de estudo: Grupo 1 - 46 indivíduos com FLP e MD; Grupo 2 - 34 indivíduos com FLP e sem MD; Grupo 3 - 34 indivíduos sem FLP e com MD; Grupo 4 - 51 indivíduos sem FLP e MD. Foi realizada a extração do DNA genômico das amostras de saliva, seguida da Reação em Cadeia da Polimerase, sequenciamento direto dos éxons 2, 3, 4, 5, 6 e 7 do gene AMELX e genotipagem dos SNPs rs3796703, rs3796704, rs3796705, rs7671281, rs2609428 e rs35951442 no gene ENAM. Para a análise estatística dos resultados foi utilizado o Teste Exato de Fisher e o Teste do Qui-quadrado de Pearson. Em relação ao sequenciamento direto do gene AMELX, mutações foram encontradas em 30,4% (n=14), 35,3% (n=12), 11,8% (n=4) e 13,7% (n=7) dos indivíduos dos Grupos 1, 2, 3 e 4, respectivamente. Trinta e sete mutações foram detectadas e distribuídas ao longo dos éxons 2 (1 mutação - 2,7%), 6 (30 mutações - 81,08%) e 7 (6 mutações - 16,22%) do gene AMELX. Houve um aumento significativo (p=0,003) na frequência de mutações nos indivíduos com FLP (Grupos 1 e 2 - 65,7%) em relação aos indivíduos sem FLP (Grupos 3 e 4 - 25,5%). Em relação às 30 mutações encontradas no éxon 6, 43,34% (n=13), 23,33% (n=7), 13,33% (n=4) e 20% (n=6) foram encontrados nos Grupos 1, 2, 3 e 4, respectivamente. A mutação silenciosa c.261C>T (rs2106416) foi detectada em 26 indivíduos distribuídos nos quatro grupos estudados, sendo significativamente mais encontrada (p=0,003) nos grupos com FLP (23,75%), em comparação com os...


The purpose of this study was to investigate the occurrence of mutations and polymorphisms (SNPs) in candidate genes to defects in the formation of enamel in individuals with cleft lip and palate (CLP) unilateral or bilateral incisive transforame isolated and associate genotype-phenotype of individuals with CLP and dental malformation (DM) in permanent teeth maxillary central incisors. For analysis of the proposed genes, saliva samples from 165 individuals from 6 to 15 years old, of both genders, were collected and divided into 4 groups: Group 1 - 46 individuals with CLP and DM; Group 2 - 34 individuals with CLP and without DM; Group 3 - 34 subjects without CLP and DM; Group 4 - 51 subjects without CLP and DM. Extraction of genomic DNA from saliva samples was performed, followed by Polymerase Chain Reaction, direct sequencing of 2, 3, 4, 5, 6 and 7 exons of AMELX gene and genotyping of SNPs rs3796703, rs3796704, rs3796705, rs7671281, rs2609428 and rs35951442 in the ENAM gene. For statistical analysis we used the Fisher's exact test and Pearson's chi-square test. Regarding direct sequencing of AMELX gene, mutations were found in 30.4% (n=14), 35.3% (n=12), 11.8% (n=4) and 13.7% (n=7) of individuals in Groups 1, 2, 3 and 4, respectively. Thirty-seven mutations were detected and distributed over the exons 2 (1 mutation - 2.7%), 6 (30 mutations - 81.08%) and 7 (6 mutations - 16.22%) of AMELX gene. There was a significant increase (p=0.003) in the frequency of mutations in individuals with CLP (Groups 1 and 2 - 65.7%) compared to subjects without CLP (Groups 3 and 4 - 25.5%). Regarding the 30 mutations found in exon 6, 43.34% (n=13), 23.33% (n=7), 13.33% (n=4) and 20% (n=6) were found in Groups 1, 2, 3 and 4, respectively. The c.261C>T silent mutation (rs2106416) was detected in 26 individuals distributed in all groups studied, and was significantly more found (p=0.003) in the groups with CLP (23.75%) compared to the groups without CLP (8.23%). In groups without...


Subject(s)
Humans , Male , Female , Child , Adolescent , Tooth Abnormalities/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Polymorphism, Genetic/genetics , Amelogenin/genetics , Exons/genetics , Genetic Association Studies , Genetic Markers , Genotype , Mutation , Polymerase Chain Reaction , Saliva
19.
Bauru; s.n; 2015. 108 p. ilus, tab, graf.
Thesis in Portuguese | LILACS | ID: lil-773793

ABSTRACT

O propósito deste trabalho foi investigar a ocorrência de mutações e polimorfismos em genes candidatos aos defeitos na formação do esmalte dentário em indivíduos com fissura labiopalatina (FLP) transforame incisivo unilateral ou bilateral isolada e associar o genótipo-fenótipo dos indivíduos com FLP e malformação dentária (MD) nos dentes incisivos centrais superiores permanentes. Foram coletadas amostras de saliva de 165 indivíduos de 6 a 15 anos de idade, de ambos os sexos, divididos em 4 grupos de estudo: Grupo 1 - 46 indivíduos com FLP e MD; Grupo 2 - 34 indivíduos com FLP e sem MD; Grupo 3 - 34 indivíduos sem FLP e com MD; Grupo 4 - 51 indivíduos sem FLP e MD. Foi realizada a extração do DNA genômico das amostras de saliva, seguida da Reação em Cadeia da Polimerase, sequenciamento direto dos éxons 2, 3, 4, 5, 6 e 7 do gene AMELX e genotipagem dos SNPs rs3796703, rs3796704, rs3796705, rs7671281, rs2609428 e rs35951442 no gene ENAM. Para a análise estatística dos resultados foi utilizado o Teste Exato de Fisher e o Teste do Qui-quadrado de Pearson. Em relação ao sequenciamento direto do gene AMELX, mutações foram encontradas em 30,4% (n=14), 35,3% (n=12), 11,8% (n=4) e 13,7% (n=7) dos indivíduos dos Grupos 1, 2, 3 e 4, respectivamente. Trinta e sete mutações foram detectadas e distribuídas ao longo dos éxons 2 (1 mutação - 2,7%), 6 (30 mutações - 81,08%) e 7 (6 mutações - 16,22%) do gene AMELX. Houve um aumento significativo (p=0,003) na frequência de mutações nos indivíduos com FLP (Grupos 1 e 2 - 65,7%) em relação aos indivíduos sem FLP (Grupos 3 e 4 - 25,5%). Em relação às 30 mutações encontradas no éxon 6, 43,34% (n=13), 23,33% (n=7), 13,33% (n=4) e 20% (n=6) foram encontrados nos Grupos 1, 2, 3 e 4, respectivamente. A mutação silenciosa c.261C>T (rs2106416) foi detectada em 26 indivíduos distribuídos nos quatro grupos estudados, sendo significativamente mais encontrada (p=0,003) nos grupos com FLP (23,75%)...


The purpose of this study was to investigate the occurrence of mutations and polymorphisms (SNPs) in candidate genes to defects in the formation of enamel in individuals with cleft lip and palate (CLP) unilateral or bilateral incisive transforame isolated and associate genotype-phenotype of individuals with CLP and dental malformation (DM) in permanent teeth maxillary central incisors. For analysis of the proposed genes, saliva samples from 165 individuals from 6 to 15 years old, of both genders, were collected and divided into 4 groups: Group 1 - 46 individuals with CLP and DM; Group 2 - 34 individuals with CLP and without DM; Group 3 - 34 subjects without CLP and DM; Group 4 - 51 subjects without CLP and DM. Extraction of genomic DNA from saliva samples was performed, followed by Polymerase Chain Reaction, direct sequencing of 2, 3, 4, 5, 6 and 7 exons of AMELX gene and genotyping of SNPs rs3796703, rs3796704, rs3796705, rs7671281, rs2609428 and rs35951442 in the ENAM gene. For statistical analysis we used the Fisher's exact test and Pearson's chi-square test. Regarding direct sequencing of AMELX gene, mutations were found in 30.4% (n=14), 35.3% (n=12), 11.8% (n=4) and 13.7% (n=7) of individuals in Groups 1, 2, 3 and 4, respectively. Thirty-seven mutations were detected and distributed over the exons 2 (1 mutation - 2.7%), 6 (30 mutations - 81.08%) and 7 (6 mutations - 16.22%) of AMELX gene. There was a significant increase (p=0.003) in the frequency of mutations in individuals with CLP (Groups 1 and 2 - 65.7%) compared to subjects without CLP (Groups 3 and 4 - 25.5%). Regarding the 30 mutations found in exon 6, 43.34% (n=13), 23.33% (n=7), 13.33% (n=4) and 20% (n=6) were found in Groups 1, 2, 3 and 4, respectively. The c.261C>T silent mutation (rs2106416) was detected in 26 individuals distributed in all groups studied, and was significantly more found (p=0.003) in the groups with CLP (23.75%) compared to the groups without CLP (8.23%). In groups without...


Subject(s)
Humans , Male , Female , Child , Adolescent , Tooth Abnormalities/genetics , Cleft Lip/genetics , Cleft Palate/genetics , Polymorphism, Genetic/genetics , Amelogenin/genetics , Exons/genetics , Genetic Association Studies , Genetic Markers , Genotype , Mutation , Polymerase Chain Reaction , Saliva
20.
Article in English | IMSEAR | ID: sea-154535

ABSTRACT

Context: Non-syndromic cleft lip/palate (NSCL/P) is a congenital anomaly with significant medical, psychological and social ramifications. There is sufficient evidence to hypothesize that locus for this condition can be identified by candidate genes. Aims: The aim of this study is to amplify the chosen region (799 G >T) of MSX 1 gene, investigate the degree of association and perform a mutation research from Raichur cleft lip and palate patient sample. Settings and Design: Case history and clinical examination of the patient were recorded to rule. Written consent was obtained from patients and controls for in vivo study. Study was designed in four steps as follows: Collection of a blood sample Genomic deoxyribonucleic acid (DNA) extraction Polymerase chain reaction (PCR) Restriction fragment length polymorphism (RFLP). Materials and Methods: Blood samples were collected from 50 subjects having NSCL/P and 50 controls. Genomic DNA was extracted, PCR and RFLP was performed for digestion products that were evaluated. Statistical Analysis: Chi-square test with P value at 95% confidence intervals. Results: The results showed a positive correlation between MSX 1 799 G >T gene variant and NSCL/P patients in Raichur patients. Conclusions: From a genetically diverse etiology MSX 1 799 G >T gene variant may be a good screening marker for NSCL/P in Raichur patients.


Subject(s)
Cleft Palate/genetics , Humans , /genetics , Patients , Polymerase Chain Reaction
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