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@#Congenital cleft lip and/or palate (CL/P) is a common malformation of maxillofacial development. At present, it is believed that the etiology of congenital cleft lip and palate mainly results from genetic factors and environmental factors. Epigenetic changes induced by environmental factors may be the key factor in the occurrence of fetal congenital malformations. As one of the important epigenetic modifications, DNA methylation has been widely and deeply studied in many fields, but as a link between the individual and the environment, its application in CL/P is limited. Existing studies have shown that DNA methylation is closely related to the occurrence of cleft lip and palate. Stimulation of folate deficiency, smoking, pollutant exposure and other environmental factors can induce changes in the state of DNA methylation, thus affecting gene expression in the development of lip and palate and leading to the occurrence of deformities.
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 , GenotypeABSTRACT
@#Normal development of the velopharyngeal structures is key to obtaining good velopharyngeal closure. In the assessment of velopharyngeal closure and normal pronunciation, a variety of instruments can be used to detect and assist in the diagnosis of velopharyngeal dysfunction. In the past, the assessment of velopharyngeal closure often used two-dimensional imaging or relied solely on the subjective assessment of the phonetician. With the development of science and technology, magnetic resonance imaging (MRI) has become widely used in the evaluation of velopharyngeal structures and functions as an ideal examination method. This article reviews the current capabilities and limitations in evaluating velopharyngeal closure, as well as recent research on the structures and functions of the velopharyngeal using static MRI, dynamic MRI, three-dimensional MRI reconstructions and diffusion tensor imaging (DTI) techniques; in addition, this work explores the role and significance of MRI technology in evaluating the structures and functions of the velopharyngeal. A review of the literature shows that static MRI is simple in terms of the scanning mode, has easily adjustable parameters, and clearly shows the anatomical structures of palatopharyngeal in resting or transient vocal states. Dynamic MRI can capture the anatomical changes of the palatopharyngeal in a more complex pronunciation state and obtain accurate dynamic images of the velopharyngeal closure process for the study of speech pathology. Three-dimensional MRI reconstructions are usually used in fine scanning of the velopharyngeal structures in a resting state; although this method takes a long time, the images obtained are clear and reliable. This approach can be used for three-dimensional reconstruction analysis and three-dimensional finite element analysis, and it can be used to help plan an operation and evaluate the effect of the surgery. DTI is a new method for observing the contractile function of muscles by observing the locus of water molecules in muscles. DTI can be used to analyze and study many muscles involved in velopharyngeal closure.
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@#Normal embryonic development is regulated by different genes and related signaling pathways. In recent years, the association between different genes and genes, genes and signaling pathways in the same organization has been widely concerned by scholars at home and abroad. Sp and Wnt gene deletion or mutation can lead to abnormal embryonic development. The results of this review indicate that abnormal embryonic development is due to Sp gene deletion/mutation The zinc finger protein superfamily member Sp1-9 is involved in the development of various tissues and organs , such as the hematopoietic system, respiratory system and skeletal system, and its deletion or mutation can lead to developmental abnormalities in embryonic tissues. In addition, the Sp8 gene is associated with the occurrence of cleft palate. By summarizing the observations about the relationship between the Wnt gene and cleft lip and palate in recent years, we can understand the abnormal expression of Wnt3, Wnt3A, Wnt5A, Wnt9B, Wnt10A and Wnt11 in humans. The occurrence of cleft lip and palate is closely related; Sp5/8 is a key downstream effector of the Wnt signaling pathway during embryonic development and participates in the Wnt signaling pathway. Sp5/8 and the Wnt signaling pathway are involved in the regulation of normal neural crest development and the self-renewal of embryonic stem cells in embryonic mice. In summary, this paper proposes that the Sp and Wnt genes may be involved in the regulation of the formation and occurrence of embryonic cleft palate and provides a reference for further study of the associated mechanisms between the two genes in the cleft palate model.