A Novel CDH1 Mutation Causing Reduced E-Cadherin Dimerization Is Associated with Nonsyndromic Cleft Lip With or Without Cleft Palate

被引:6
作者
Du, Shiyue [1 ]
Yang, Yujie [2 ,3 ]
Yi, Ping [1 ]
Luo, Junyu [1 ]
Liu, Teng [1 ]
Chen, Rui [1 ]
Liu, Chun-jie [1 ]
Ma, Tingbin [1 ]
Li, Yulei [1 ]
Wang, Cheng [1 ]
Weng, Jun [1 ]
Liu, Mugen [1 ]
Zhang, Luoying [1 ]
Yang, Baosheng [4 ]
Zeng, Xiaomei [1 ]
Liu, Jing Yu [1 ]
机构
[1] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Ctr Human Genome Res, Key Lab Mol Biophys,Minist Educ, Wuhan 430074, Hubei, Peoples R China
[2] Fudan Univ, Huashan Hosp, Dept Neurol, Shanghai, Peoples R China
[3] Fudan Univ, Huashan Hosp, Natl Clin Res Ctr Aging & Med, Shanghai, Peoples R China
[4] Xinxiang Med Univ, Sanquan Coll, Xinxiang, Henan, Peoples R China
基金
美国国家科学基金会; 中国国家自然科学基金;
关键词
NSCL; P; CDH1; E-cadherin dimerization; cell-cell adhesion ability; DIFFUSE GASTRIC-CANCER; PREDISPOSING GENE CDH1; GERMLINE MUTATIONS; RARE VARIANTS; ORAL CLEFTS; IDENTIFICATION; ADHESIVE; FAMILIES; RISK;
D O I
10.1089/gtmb.2019.0092
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aims: Cleft lip with or without cleft palate (CL/P) is a common birth defect with the average prevalence of 1/700 to 1/1000. Almost 70% of CL/P patients belong to nonsyndromic CL/P (NSCL/P). The aim of this study was to identify the underlying cause of a four-generation Chinese family with autosomal dominant NSCL/P. Methods: Genomic DNA was extracted from peripheral blood leukocytes, and whole-exome sequencing was carried out to identify the underlying genetic cause of the disorder. The mutation was confirmed by Sanger sequencing and polymerase chain reaction-restriction fragment length polymorphism method. Western blotting and coimmunoprecipitation were used to analyze the protein expression level and adhesive dimerization of the CDH1 mutants. Slow aggregation assays were conducted to investigate the cell-cell adhesion ability. Results: A novel missense mutation (c.468G>C/p.Trp156Cys) of CDH1 was identified in the proband and the mutation was shown to cosegregate with the phenotype in the family. Furthermore, we found that the p.Trp156Cys mutation led to decreased E-cadherin dimerization and cell-cell adhesion ability. Conclusions: Our findings identified a novel CDH1 variant (c.468G>C/p.Trp156Cys) responsible for NSCL/P in a Chinese family, which expanded the mutational spectrum of CDH1 gene and may contribute to understanding the molecular basis of NSCL/P.
引用
收藏
页码:759 / 765
页数:7
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