泰国人群中与腭裂相关的CDH1（E-钙黏蛋白）基因变体

Variants of the CDH1 (E-Cadherin) Gene Associated with Oral Clefts in the Thai Population.

作者信息

Ittiwut Rungnapa, Ittiwut Chupong, Siriwan Pichit, Chichareon Vichai, Suphapeetiporn Kanya, Shotelersuk Vorasuk

机构信息

1 Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University , Bangkok, Thailand .

2 Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital , the Thai Red Cross Society, Bangkok, Thailand .

出版信息

Genet Test Mol Biomarkers. 2016 Jul;20(7):406-9. doi: 10.1089/gtmb.2015.0325. Epub 2016 May 26.

DOI:10.1089/gtmb.2015.0325

PMID:27227907

Abstract

OBJECTIVE

The etiology of oral clefts in humans is genetically complex and mutations in multiple genes have been linked with clefting. CDH1 (E-cadherin) has been found to be involved in lip and palate development, and CDH1 mutations are associated with oral clefts in some populations.

MATERIALS AND METHODS

To determine if there is an association between CDH1 and oral clefting in a Thai population, we sequenced the entire 6.5-kb coding region of the CDH1 gene in 80 oral cleft patients and compared the identified variants with those found in 138 unrelated Thai individuals who did not have oral clefts, as genotyped by exome sequencing.

RESULTS

Among the oral cleft patients, four nonsynonymous single nucleotide variants (SNVs), c.1235T>C (p.V412A), c.1273G>A (p.V425I), c.1565C>T (p.T522I), and c.1888C>G (p.L630V), were identified. Only one nonsynonymous variant (c.1409C>T; p.T470I) was found among the 138 noncleft exomes. The frequency of nonsynonymous SNVs on the CDH1 gene in oral cleft patients (4/80) was significantly higher than that in the control group (1/138) (p = 0.042).

CONCLUSION

We found that nonsynonymous variants of CDH1 were associated with oral clefts in the Thai population.

摘要

目的

人类口腔裂隙的病因在遗传上较为复杂，多个基因的突变与裂隙形成有关。已发现CDH1（E-钙黏蛋白）参与唇和腭的发育，并且在某些人群中，CDH1突变与口腔裂隙相关。

材料与方法

为了确定泰国人群中CDH1与口腔裂隙之间是否存在关联，我们对80例口腔裂隙患者的CDH1基因整个6.5kb的编码区进行了测序，并将鉴定出的变异与138名无口腔裂隙的无关泰国个体（通过外显子组测序进行基因分型）中发现的变异进行比较。

结果

在口腔裂隙患者中，鉴定出四个非同义单核苷酸变异（SNV），即c.1235T>C（p.V412A）、c.1273G>A（p.V425I）、c.1565C>T（p.T522I）和c.1888C>G（p.L630V）。在138个非裂隙外显子组中仅发现一个非同义变异（c.1409C>T；p.T470I）。口腔裂隙患者中CDH1基因非同义SNV的频率（4/80）显著高于对照组（1/138）（p = 0.042）。