Aims: Cleft lip with or without cleft palate (CL/P) is a common birth defect with an average prevalence of 1/700 to 1/1000. Almost 70% of CL/P cases are 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 methods. 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 the CDH1 gene and may contribute to understanding the molecular basis of NSCL/P.
Keywords: CDH1; E-cadherin dimerization; NSCL/P; cell–cell adhesion ability.