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The Recurrent E-Cadherin (CDH1) Mutation c.760G>A Causes Orofacial Clefts but Does Not Predispose to Hereditary Cancer. | LitMetric

AI Article Synopsis

Article Abstract

: Congenital, non-syndromic orofacial clefts (CL/P) are infrequently monogenic in etiology. However, heterozygous pathogenic germline variants were reported in a few non-syndromic CL/P families, as well as in one syndromic form of CL/P: the blepharocheilodontic syndrome. encodes epithelial cadherin (E-cadherin), and close to 300 different pathogenic variants are listed in the ClinVar mutation database. The majority of germline variants are implicated in hereditary diffuse gastric cancer (HDGC) susceptibility. The purpose of this study was to classify the c.760G>A (p.Asp254Asn) mutation with respect to its resulting phenotype. : Exome sequencing and targeted Sanger sequencing were performed in a family segregating CL/P. A review of pathogenic variants in ClinVar and those identified in a PubMed/MEDLINE search was performed. : We identified a family with six individuals, who were 35-77 years old (mean 56 years) at their last examination, uniformly affected with bilateral CL/P. The c.760G>A variant segregated with CL/P. This variant had been reported in 21 individuals, most often children and young adults, from six families. We determined a significant sex preponderance for this variant regarding CL/P: all 16 male and 5 of 11 female heterozygotes presented with CL/P. Furthermore, none of the heterozygous individuals in seven families reported any gastrointestinal tumors. : The recurrent c.760G>A mutation confers a high risk for CL/P, with strong male preponderance. This review of 27 mutation carriers, including 3 who were 68, 70, and 77 years of age, indicates that c.760G>A does not confer an increased risk for HDGC. The relevance of differentiating craniofacial from cancer phenotypes in mutation carriers is substantial for precision medicine and for counseling families.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11594193PMC
http://dx.doi.org/10.3390/genes15111475DOI Listing

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