A Novel <i>CDH1</i> Variant Identified in a Chinese Family with Blepharocheilodontic Syndrome
Bichen Lin,
Yang Liu,
Lanxin Su,
Hangbo Liu,
Hailan Feng,
Miao Yu,
Haochen Liu
Affiliations
Bichen Lin
First Clinical Division, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
Yang Liu
Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
Lanxin Su
Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
Hangbo Liu
Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
Hailan Feng
Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
Miao Yu
Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
Haochen Liu
Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing 100081, China
The goal of the current study was to identify the pathogenic gene variant in a Chinese family with Blepharocheilodontic (BCD) syndrome. Whole-exome sequencing (WES) and Sanger sequencing were used to identify the pathogenic gene variant. The harmfulness of the variant was predicted by bioinformatics. We identified a novel heterozygous missense variant c.1198G>A (p.Asp400Asn) in the CDH1 gene in the proband and his mother with BCD syndrome. The sequencing results of three healthy individuals in this family are wild type. This result is consistent with familial co-segregation. According to ReVe, REVEL, CADD, gnomAD, dbSNP, and the classification of pathogenic variants with the standards of the 2015 American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG), c.1198G>A (p.Asp400Asn) is predicted to be a likely pathogenic. We observed that variant c.1198G>A (p.Asp400Asn) was located in the extracellular cadherin-type repeats in CDH1. Amino acid sequence alignment of the CDH1 protein among multiple species showed that Asp400 was highly evolutionarily conserved. The conformational analysis showed that this variant might cause structural damage to the CDH1 protein. Phenotypic analysis revealed unique dental phenotypes in patients with BCD syndrome, such as oligodontia, conical-shaped teeth, and notching of the incisal edges. Our results broaden the variation spectrum of BCD syndrome and phenotype spectrum of CDH1, which can help with the clinical diagnosis, treatment, and genetic counseling in relation to BCD syndrome.
