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1.
An. bras. dermatol ; 94(6): 658-663, Nov.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS (Américas) | ID: biblio-1054887

RESUMO

Abstract Background: Palmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated. Objective: The aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis. Methods: Fifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed. Results: Among the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1). Study limitation: Lack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions. Conclusions: The four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Psoríase/genética , Interleucinas/genética , Mutação , Fenótipo , Psoríase/patologia , China , Análise de Sequência de DNA , Estatísticas não Paramétricas , Grupo com Ancestrais do Continente Asiático/genética , Análise do Polimorfismo de Comprimento de Fragmentos Amplificados , Estudos de Associação Genética , Dermatoses do Pé/genética , Dermatoses do Pé/patologia , Dermatoses da Mão/genética , Dermatoses da Mão/patologia , Heterozigoto
2.
An. bras. dermatol ; 94(4): 429-433, July-Aug. 2019. tab
Artigo em Inglês | LILACS (Américas) | ID: biblio-1038308

RESUMO

Abstract: Background: Behçet disease is a prototypical systemic autoimmune disease, caused by a complex interplay between environmental and genetic factors. The transmembrane immunoglobulin and mucin domain-3 (TIM-3) is a distinct member of the TIM family that is preferentially expressed on Th1 cells and plays a role in Th1-mediated autoimmune or inflammatory diseases, such as Behçet disease. Objective: The aim of this study was to test the potential association between TIM-3 gene polymorphisms and Behçet disease. Methods: Two single-nucleotide polymorphisms of TIM-3 (rs9313439 and rs10515746) were genotyped in 212 patients with Behçet disease and 200 healthy controls. Typing of the polymorphisms was performed using multiplex PCR amplification. Results: There were no significant differences in allele and genotype frequencies between the Behçet disease patients and controls who were successfully genotyped. Similar results were also found after stratification by gender, age, or clinical features. Study limitations: Lack of studies on various racial or ethnic groups and small sample size. Conclusion: This study failed to demonstrate any association between the tested TIM-3 polymorphisms and Behçet disease.


Assuntos
Humanos , Masculino , Feminino , Adulto , Síndrome de Behçet/genética , Polimorfismo de Nucleotídeo Único , Receptor Celular 2 do Vírus da Hepatite A/genética , Estudos de Casos e Controles , Modelos Logísticos , Fatores de Risco , Medição de Risco , Alelos , Estudos de Associação Genética , Reação em Cadeia da Polimerase Multiplex , Frequência do Gene , Irã (Geográfico)
3.
Rev. ADM ; 76(3): 156-161, mayo-jun. 2019. ilus, tab
Artigo em Espanhol | LILACS (Américas) | ID: biblio-1022128

RESUMO

Durante el crecimiento y desarrollo de la cabeza, ésta lo hace en diferentes direcciones y proporciones, habiendo un límite entre la armonía /desarmonía conocido como umbral. Se hace referencia a este concepto, la forma de escribirlo y leerlo por medio de un código que lo simboliza. Objetivo: Poner al alcance de la comunidad médica un código de lectura e identificación de fenotipos craneofaciales sindrómicos y no sindrómicos. Conclusiones: Se considera que este concepto de umbral craneofacial y su código de lectura pueden ser usados en la enseñanza e investigación de la armonía-desarmonía durante el crecimiento y desarrollo de la cabeza, resultando ser de gran utilidad en la comprensión rápida y sencilla de la lectura del fenotipo craneofacial (AU)


During the growth and development of the head, it does so in different directions and proportions, there being a limit between the harmony / disharmony known as threshold. Reference is made to this concept, the way of writing it and reading it by means of a code that symbolizes it. Objective: To put within reach of the medical community, a code of reading and identification of syndromic and non-syndromic craniofacial phenotypes. Conclusions: It is considered that this concept of a craniofacial threshold and its reading code can be used in the teaching and research of harmony / disharmony during the growth and development of the head, being very useful in the quick and easy comprehension of the reading of the craniofacial phenotype (AU)


Assuntos
Humanos , Fenótipo , Herança Multifatorial , Desenvolvimento Maxilofacial , Prognatismo , Retrognatismo , Cefalometria , Anormalidades Craniofaciais/classificação , Códigos , Estudos de Associação Genética , Cabeça/crescimento & desenvolvimento , Má Oclusão/classificação
4.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-762588

RESUMO

Deletion on the short arm of chromosome 18 is a rare disorder characterized by intellectual disability, growth retardation, and craniofacial malformations (such as prominent ears, microcephaly, ptosis, and a round face). The phenotypic spectrum is wide, encompassing a range of abnormalities from minor congenital malformations to holoprosencephaly. We present a case of a 2-year-old girl with ptosis, a round face, broad neck with low posterior hairline, short stature, and panhypopituitarism. She underwent ventilation tube insertion for recurrent otitis media with effusion. Brain magnetic resonance imaging showed an ectopic posterior pituitary gland and a shallow, small sella turcica with poor visualization of the pituitary stalk. Cytogenetic and chromosomal microarray analysis revealed a de novo deletion on the short arm of chromosome 18 (arr 18p11.32p11.21[136,227–15,099,116]x1). She has been treated with recombinant human growth hormone (GH) therapy since the age of 6 months after diagnosis of GH deficiency. Her growth rate has improved without any side effects from the GH treatment. This case expands the phenotypic spectrum of 18p deletion syndrome and emphasizes the positive impact of GH therapy on linear growth in this syndrome characterized by growth deficiency. Further studies are required to define the genotype-phenotype correlation according to size and loci of the deletion in 18p deletion syndrome and to predict prognosis.


Assuntos
Braço , Encéfalo , Pré-Escolar , Cromossomos Humanos Par 18 , Citogenética , Diagnóstico , Orelha , Feminino , Estudos de Associação Genética , Hormônio do Crescimento , Holoprosencefalia , Hormônio do Crescimento Humano , Humanos , Deficiência Intelectual , Imagem por Ressonância Magnética , Análise em Microsséries , Microcefalia , Pescoço , Otite Média com Derrame , Hipófise , Neuro-Hipófise , Prognóstico , Sela Túrcica , Ventilação
5.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-741366

RESUMO

PURPOSE: Myotonic dystrophy, also known as dystrophia myotonica (DM), is an autosomal dominant disorder with 2 genetically distinct forms. DM type 1 (DM1) is the more common form and is caused by abnormal expansion of cytosine/thymine/guanine (CTG) repeats in the DM protein kinase (DMPK) gene. Our study aimed to determine whether the age of onset is correlated with CTG repeat length in a population of pediatric patients with DM1. METHODS: We retrospectively identified 30 pediatric patients with DM1 that underwent DMPK testing, of which the clinical data of 17 was sufficient. The cohort was divided into 2 subgroups based on the clinical phenotype (congenital-onset vs. late-onset) and number of CTG repeats ( < 1,000 vs. ≥1,000). RESULTS: We found no significant difference between the age of onset and CTG repeat length in our pediatric patient population. Based on clinical subgrouping, we found that the congenital-onset subgroup was statistically different with respect to several variables, including prematurity, rate of admission to neonatal intensive care unit, need for respiratory support at birth, hypotonia, dysphagia, ventilator dependence, and functional status on last visit, compared to the late-onset subgroup. Based on genetic subgrouping, we found a single variable (poor feeding in neonate) that was significantly different in the large CTG subgroup than that in the small CTG subgroup. CONCLUSION: Clinical variables exhibiting statistically significant differences between the subgroups should be focused on prognosis and designing tailored management approaches for the patients; our findings will contribute to achieve this important goal for treating patients with DM1.


Assuntos
Idade de Início , Estudos de Coortes , Transtornos de Deglutição , Estudos de Associação Genética , Genótipo , Humanos , Recém-Nascido , Terapia Intensiva Neonatal , Hipotonia Muscular , Distrofia Miotônica , Miotonina Proteína Quinase , Parto , Fenótipo , Prognóstico , Estudos Retrospectivos , Ventiladores Mecânicos
6.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-740353

RESUMO

BACKGROUND AND OBJECTIVES: Autosomal recessive non-syndromic hearing loss (ARNSHL) with genetic origin is common (1/2000 births). ARNSHL can be associated with mutations in gap junction protein beta 2 (GJB2). To this end, this cohort investigation aimed to find the contribution of GJB2 gene mutations with the genotype-phenotype correlations in 45 ARNSHL cases in the Kurdish population. SUBJECTS AND METHODS: Genomic DNA was extracted from a total of 45 ARNSHL families. The linkage analysis with 3 short tandem repeat markers linked to GJB2 was performed on 45 ARNSHL families. Only 9 of these families were linked to the DFNB1 locus. All the 45 families who took part were sequenced for confirmation linkage analysis (to perform a large project). RESULTS: A total of three different mutations were determined. Two of which [c.35delG and c.-23+1G>A (IVS1+1G>A)] were previously reported but (c.299-300delAT) mutation was novel in the Kurdish population. The homozygous pathogenic mutations of GJB2 gene was observed in nine out of the 45 families (20%), also heterozygous genotype (c.35delG/N)+(c.-23+1G>A/c.-23+1G>A) were observed in 4/45 families (8.8%). The degree of hearing loss (HL) in patients with other mutations was less severe than patients with c.35delG homozygous mutation (p < 0.001). CONCLUSIONS: Our data suggest that GJB2 mutations constitute 20% of the etiology of ARNSHL in Iran; moreover, the c.35delG mutation is the most common HL cause in the Kurdish population. Therefore, these mutations should be included in the molecular testing of HL in this population.


Assuntos
Estudos de Coortes , Conexinas , DNA , Estudos de Associação Genética , Genótipo , Perda Auditiva , Audição , Humanos , Irã (Geográfico) , Repetições de Microssatélites
7.
Laboratory Animal Research ; : 165-171, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-786407

RESUMO

Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.


Assuntos
Animais , Biologia Computacional , Genes vif , Estudos de Associação Genética , Humanos , Camundongos , Fenótipo , Biologia de Sistemas
8.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-785582

RESUMO

BACKGROUND: Primary hyperoxaluria (PH), a rare inborn error of glyoxylate meta bolism causing overproduction of oxalate, is classified into three genetic subgroups: type 1–3 (PH1–PH3) caused by AGXT, GRHPR , and HOGA1 gene mutations, respectively. We performed a retrospective case series study of Korean pediatric patients with PH.METHODS: In total, 11 unrelated pediatric patients were recruited and their phenotypes and genotypes were analyzed by a retrospective review of their medical records.RESULTS: Mutational analyses revealed biallelic AGXT mutations (PH1) in nine patients and a single heterozygous GRHPR and HOGA1 mutation in one patient each. The c.33dupC was the most common AGXT mutation with an allelic frequency of 44%. The median age of onset was 3 months (range, 2 months-3 years), and eight patients with PH1 presented with end stage renal disease (ESRD). Patients with two truncating mutations showed an earlier age of onset and more frequent retinal involvement than patients with one truncating mutation. Among eight PH1 patients presenting with ESRD, five patients were treated with intensive dialysis followed by liver transplantation (n=5) with/without subsequent kidney transplantation (n=3).CONCLUSION: Most patients presented with severe infantile forms of PH. Patients with two truncating mutations displayed more severe phenotypes than those of patients with one truncating mutation. Sequential liver and kidney transplantation was adopted for PH1 patients presenting with ESRD. A larger nation-wide multicenter study is needed to confirm the genotype-phenotype correlations and outcomes of organ transplantation.


Assuntos
Idade de Início , Diálise , Estudos de Associação Genética , Genótipo , Humanos , Concentração de Íons de Hidrogênio , Hiperoxalúria Primária , Falência Renal Crônica , Transplante de Rim , Fígado , Transplante de Fígado , Registros Médicos , Transplante de Órgãos , Fenótipo , Retinaldeído , Estudos Retrospectivos , Transplantes
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-776825

RESUMO

OBJECTIVE@#To explore the genetic basis of a child featuring intellectual disability, developmental delay and epilepsy.@*METHODS@#Cytogenetic and molecular analysis including chromosomal karyotyping analysis, single nucleotide polymorphism array (SNP array) and qPCR were performed.@*RESULTS@#The karyotype of the child was determined as 46, XX; SNP array: arr [19]21q22.12q22.13(36 860 195-38 801 482)×1 dn. A heterozygous 1.9 Mb microdeletion was detected at 21q22.12q22.13. qPCR has confirmed deletion of exon 1 of the DYRK1A gene, which has occurred de novo.@*CONCLUSION@#A 21q22 deletion was diagnosed with multiple genetic methods. Genotype-phenotype correlation suggested DYRK1A to be a candidate for intellectual disability.


Assuntos
Criança , Deficiências do Desenvolvimento , Genética , Epilepsia , Genética , Estudos de Associação Genética , Humanos , Deficiência Intelectual , Genética , Cariotipagem , Proteínas Serina-Treonina Quinases , Genética , Proteínas Tirosina Quinases , Genética , Deleção de Sequência
10.
Laboratory Medicine Online ; : 224-231, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-760514

RESUMO

MYH9-related disorders (MYH9RD) are autosomal-dominant disorders characterized by macrothrombocytopenia with or without leukocyte inclusion bodies or extra-hematological features, such as sensorineural deafness and renal impairment. MYH9RD can be misdiagnosed as an acquired form of thrombocytopenia including immune thrombocytopenic purpura (ITP). This leads to delayed diagnosis or administration of ineffective treatment. In the present study, we investigated the clinical and molecular characteristics of five unrelated Korean patients with MYH9RD and their family members, from four institutions. We reviewed clinical and laboratory data including extra-hematological manifestations. MYH9 pathogenic variants were detected by direct sequencing in all probands and the affected family members (N=10): two probands with c.5521G>A (p.Glu1841Lys) and one proband each with c.99G>T (p.Trp33Cys), c.287C>T (p.Ser96Leu), and c.3493C>T (p.Arg1165Cys). All patients had macrothrombocytopenia. Only the proband with Ser96Leu had extra-hematological manifestations. Past history revealed that two patients had been misdiagnosed with ITP and one of them had received a splenectomy. We validated the frequency of misdiagnosis (~20%) and genotype-phenotype correlations through a comprehensive review of previously reported cases of MYH9RD in Korea. It is important to suspect MYH9RD in patients with thrombocytopenia, and timely identification of macrothrombocytopenia and MYH9 pathogenic variants is required for early and accurate diagnosis of MYH9RD.


Assuntos
Surdez , Diagnóstico Tardio , Diagnóstico , Erros de Diagnóstico , Estudos de Associação Genética , Humanos , Corpos de Inclusão , Coreia (Geográfico) , Leucócitos , Púrpura Trombocitopênica Idiopática , Esplenectomia , Trombocitopenia
11.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-719693

RESUMO

For the past three decades, a large number of genetic studies have been performed to examine genetic variants associated with asthma and its subtypes in hopes of gaining better understanding of the mechanisms underlying disease pathology and to identify genetic biomarkers predictive of disease outcomes. Various methods have been used to achieve these objectives, including linkage analysis, candidate gene polymorphism analysis, and genome-wide association studies (GWAS); however, the degree to which genetic variants contribute to asthma pathogenesis has proven to be much less significant than originally expected. Subsequent application of GWAS to well-defined phenotypes, such as occupational asthma and non-steroidal anti-inflammatory drugexacerbated respiratory diseases, has overcome some of these limitations, although with only partial success. Recently, a combinatorial analysis of single nucleotide polymorphisms (SNPs) identified by GWAS has been used to develop sets of genetic markers able to more accurately stratify asthma subtypes. In this review, we discuss the implications of the identified SNPs in diagnosis of asthma and its subtypes and the progress being made in combinatorial analysis of genetic variants.


Assuntos
Anti-Inflamatórios não Esteroides , Aspirina , Asma , Asma Ocupacional , Biomarcadores , Diagnóstico , Estudos de Associação Genética , Marcadores Genéticos , Técnicas Genéticas , Estudo de Associação Genômica Ampla , Esperança , Patologia , Fenótipo , Polimorfismo de Nucleotídeo Único
12.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-741914

RESUMO

OBJECTIVE: Ubiquitin-specific peptidase 46 gene (USP46) polymorphisms is part of ubiquitin-proteasome system, which is responsible for dynamic cellular processes such as the regulation of cell cycle. USP46 has been reported to be associated with major depressive disorder. The objective of the present study was to investigate the association of USP46 polymorphisms with affective temperamental traits in healthy subjects. METHODS: A total of 557 Korean healthy volunteers were recruited, and 545 subjects (328 male, 217 female) were included in the final analysis. The DNA of the subjects was isolated from saliva samples. Two single-nucleotide polymorphisms (SNPs) rs346005, rs2244291 in USP46 were genotyped. Affective temperaments were assessed using the Korean version of Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Autoquestionnaire (TEMPS-A). RESULTS: A significant association was found between rs346005 genotypes and TEMPS-A only in male subjects. In particular, subjects with the CC genotype of rs346005 showed a more depressive temperament than subjects with AA or CA genotypes in males. For rs2244291, there were no associations between the rs2244291 genotypes and TEMPS-A scores. CONCLUSION: Some affective temperaments may serve as a genetic predisposing factors for affective disorders, such as depressive disorder, via vulnerability genes related to the ubiquitin-proteasome system.


Assuntos
Causalidade , Ciclo Celular , Transtorno Depressivo , Transtorno Depressivo Maior , DNA , Estudos de Associação Genética , Genótipo , Voluntários Saudáveis , Humanos , Masculino , Transtornos do Humor , Saliva , Temperamento , Voluntários
13.
Chinese Medical Journal ; (24): 145-153, 2019.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-772868

RESUMO

BACKGROUND@#Osteogenesis imperfecta (OI), a heritable bone fragility disorder, is mainly caused by mutations in COL1A1 gene encoding α1 chain of type I collagen. This study aimed to investigate the COL1A1 mutation spectrum and quantitatively assess the genotype-phenotype relationship in a large cohort of Chinese patients with OI.@*METHODS@#A total of 161 patients who were diagnosed as OI in Department of Endocrinology of Peking Union Medical College Hospital from January 2010 to December 2017 were included in the study. The COL1A1 mutation spectrum was identified by next generation sequencing and confirmed by Sanger sequencing. A new clinical scoring system was developed to quantitatively assess the clinical severity of OI and the genotype-phenotype relationship was analyzed. The independent sample t-test, analysis of variance, Mann-Whitney U-test, Chi-squared test, Pearson correlation, and multiple linear regression were applied for statistical analyses.@*RESULTS@#Among 161 patients with OI, 32.9% missense mutations, 16.8% non-sense mutations, 24.2% splice-site mutations, 24.8% frameshift mutations, and 1.2% whole-gene deletions were identified, of which 38 variations were novel. These mutations led to 53 patients carrying qualitative defects and 67 patients carrying quantitative defects in type I collagen. Compared to patients with quantitative mutations, patients with qualitative mutations had lower alkaline phosphatase level (296 [132, 346] U/L vs. 218 [136, 284] U/L, P = 0.009) and higher clinical score (12.2 ± 5.3 vs. 7.4 ± 2.4, P < 0.001), denoting more severe phenotypes including shorter stature, lower bone mineral density, higher fracture frequency, more bone deformity, vertebral compressive fractures, limited movement, and dentinogenesis imperfecta (DI). Patients would not present with DI if the glycine substitutions happened before the 79th amino acid in triple helix of α1 chains.@*CONCLUSIONS@#This presented distinctive COL1A1 mutation spectrum in a large cohort of Chinese patients with OI. This new quantitative analysis of genotype-phenotype correlation would be helpful to predict the prognosis of OI and genetic counseling.


Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Colágeno Tipo I , Genética , Feminino , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Mutação , Genética , Osteogênese Imperfeita , Genética , Patologia , Adulto Jovem
14.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-777615

RESUMO

BACKGROUND@#Hypertension and atherosclerosis are bidirectionally related, while platelet count could serve as an indicator of endothelial repair. Therefore, high platelet counts could be associated with hypertension by indicating more intense endothelial repair activity. Furthermore, short stature has been shown to constitute a risk of atherosclerosis. Since inflammation-related single-nucleotide polymorphism (SNP (rs3782886)) is reportedly associated with myocardial infarction and short stature, rs3782886 could be associated with a high platelet count and thus more intense endothelial repair activity.@*METHODS@#We conducted a cross-sectional study of 988 elderly Japanese who participated in a general health check-up. Short stature was defined as a height of at or under the 25th percentile of the study population, and high platelet count as the highest tertiles of the platelet levels.@*RESULTS@#High platelet counts were found to be independently and positively associated with hypertension while rs3782886 was independently associated with high platelet levels and short stature. The classical cardiovascular risk factor-adjusted odds ratio (OR) and 95% confidence interval (CI) of high platelet count for hypertension was 1.34 (1.02, 1.77). With non-minor homo of the rs3782886 as the reference group, the adjusted OR and 95% CI for high platelet count and short stature of minor home were 2.40 (1.30, 4.42) and 2.21 (1.16, 4.21), respectively.@*CONCLUSION@#SNP (rs3782886) was shown to be associated with high platelet count and short stature. This result partly explains how a genetic factor can influence the impact of height on endothelial repair.


Assuntos
Idoso , Idoso de 80 Anos ou mais , Plaquetas , Metabolismo , Estatura , Genética , Estudos Transversais , Endotélio Vascular , Fisiologia , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Hipertensão , Sangue , Epidemiologia , Genética , Masculino , Pessoa de Meia-Idade , Razão de Chances , Contagem de Plaquetas , Polimorfismo de Nucleotídeo Único
15.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wprim-771977

RESUMO

With the advance of high-throughout sequencing technology and its extensive application in clinical diagnosis, analysis of sequencing data has become an important part of clinical diagnosis. To date, the development and establishment of various software and databases have made it convenient to extract useful information from massive amounts of high-throughput sequencing data. However, it is still a challenge for correlating the clinical-genetic diagnosis based on the above-mentioned sequence data with the screened DNA variations and disease phenotypes. Further validation of the proposed pathogenesis with the discovered molecular defects are required. Here a comprehensive review is provided for the strategies of sequencing data analysis, commonly used phenotype-genotype correlation tools, and functional analysis and verification methods for the genetic diagnosis.


Assuntos
Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Fenótipo , Análise de Sequência de DNA , Software
16.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-739674

RESUMO

The rapid increase in genetic dataset volume has demanded extensive adoption of biological knowledge to reduce the computational complexity, and the biological pathway is one well-known source of such knowledge. In this regard, we have introduced a novel statistical method that enables the pathway-based association study of large-scale genetic dataset—namely, PHARAOH. However, researcher-level application of the PHARAOH method has been limited by a lack of generally used file formats and the absence of various quality control options that are essential to practical analysis. In order to overcome these limitations, we introduce our integration of the PHARAOH method into our recently developed all-in-one workbench. The proposed new PHARAOH program not only supports various de facto standard genetic data formats but also provides many quality control measures and filters based on those measures. We expect that our updated PHARAOH provides advanced accessibility of the pathway-level analysis of large-scale genetic datasets to researchers.


Assuntos
Conjunto de Dados , Estudos de Associação Genética , Métodos , Controle de Qualidade
17.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-775170

RESUMO

BACKGROUND@#Both aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and lifestyle behaviors are involved in coronary artery disease (CAD), while the interaction between them is currently unknown.@*METHODS@#A nested case-control study was conducted in 161 patients with CAD and 495 controls in dyslipidemia population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013. Anthropometric data and blood samples were collected, demographic characteristics and lifestyle behaviors information were obtained by a face-to-face interview, dietary intake was assessed by a food frequency questionnaire, and genomic DNA was genotyped.@*RESULTS@#Carriers with increasing number of A alleles had an elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI = 1.114-1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036-2.148). Similarly, individuals with rs671 A/A genotype had a higher CAD risk than individuals with A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139-4.101). We found a borderline additive interaction between regular fried food intake and A/A and A/G genotypes, and a significantly additive interaction between sedentary/light physical activity and A/A and A/G genotypes.@*CONCLUSIONS@#Individuals with A/A or A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and take fried food regularly, than individuals with G/G genotypes. These findings can help to provide a guide to targeted heart health management.


Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Aldeído-Desidrogenase Mitocondrial , Genética , Alelos , Estudos de Casos e Controles , China , Doença da Artéria Coronariana , Sangue , Genética , Dislipidemias , Sangue , Genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Risco
18.
Laboratory Medicine Online ; : 119-124, 2018.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-715907

RESUMO

Pathogenic variants of bone morphogenic protein receptor type 2 gene (BMPR2) are related to the majority of cases of heritable pulmonary arterial hypertension (PAH). Over 400 pathogenic variants have been identified. However, clinical characterization of PAH is still incomplete. We present a case of heritable PAH in a Korean family showing serious clinical presentation with high penetrance. Genetic sequencing revealed a known heterozygous BMPR2 pathogenic variant, c.418+5G>A, at a splice site of intron 3. Serious clinical presentation with high penetrance suggested that the interplay of other factors with pathologic variants might be in genotype-phenotype correlation. Further studies are needed to clarify these issues for the development of personalized medicine approaches for PAH.


Assuntos
Hipertensão Pulmonar Primária Familiar , Estudos de Associação Genética , Humanos , Hipertensão , Hipertensão Pulmonar , Íntrons , Penetrância , Medicina de Precisão , Artéria Pulmonar
19.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-714432

RESUMO

BACKGROUND: The major genetic cause of Currarino syndrome (CS), a congenital malformation syndrome typically characterized by sacral agenesis, anorectal malformation, and presence of a pre-sacral mass, is known to be pathogenic variants in motor neuron and pancreas homeobox 1 (MNX1), which exist in almost all familial cases and 30% of sporadic cases. Less commonly, a large deletion or a complex rearrangement involving the 7q36 region is associated with CS. We investigated the spectrum of MNX1 pathogenic variants and associated clinical features in the Korean patients with CS. METHODS: We enrolled 25 patients with CS, including 24 sporadic cases and one familial case. Direct sequencing of MNX1 and multiplex ligation-dependent probe amplification were performed. We also analyzed clinical phenotypes and evaluated genotype-phenotype correlations. RESULTS: We identified six novel variants amongst a total of six null variants, one missense variant, and one large deletion. The null variants included four frameshift variants (p.Gly98Alafs*124, p.Gly145Alafs*77, p.Gly151Leufs*67, and p.Ala216Profs*5) and two nonsense variants (p.Tyr186* and p.Gln212*). The missense variant, p.Lys295Gln, was located in the highly-conserved homeobox domain and was predicted to be deleterious. A large deletion involving the 7q36 region was detected in one patient. Pathogenic variants in MNX1 were detected in 28% of all CS cases and 25% of sporadic cases. The clinical phenotype was variable in patients with and without pathogenic variants; no significant genotype-phenotype correlation was observed. CONCLUSIONS: This study revealed the spectrum and phenotypic variability of MNX1 pathogenic variants in the Korean population.


Assuntos
Genes Homeobox , Estudos de Associação Genética , Humanos , Neurônios Motores , Reação em Cadeia da Polimerase Multiplex , Pâncreas , Fenótipo
20.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wprim-714076

RESUMO

Recent advances in genetics have determined that a number of epilepsy syndromes that occur in the first year of life are associated with genetic etiologies. These syndromes range from benign familial epilepsy syndromes to early-onset epileptic encephalopathies that lead to poor prognoses and severe psychomotor retardation. An early genetic diagnosis can save time and overall cost by reducing the amount of time and resources expended to reach a diagnosis. Furthermore, a genetic diagnosis can provide accurate prognostic information and, in certain cases, enable targeted therapy. Here, several early infantile epilepsy syndromes with strong genetic associations are briefly reviewed, and their genotype-phenotype correlations are summarized. Because the clinical presentations of these disorders frequently overlap and have heterogeneous genetic causes, next-generation sequencing (NGS)-based gene panel testing represents a more powerful diagnostic tool than single gene testing. As genetic information accumulates, genetic testing will likely play an increasingly important role in diagnosing pediatric epilepsy. However, the efforts of clinicians to classify phenotypes in nondiagnosed patients and improve their ability to interpret genetic variants remain important in the NGS era.


Assuntos
Encefalopatias , Diagnóstico , Epilepsia , Estudos de Associação Genética , Testes Genéticos , Genética , Humanos , Lactente , Fenótipo , Prognóstico
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