A novel pathogenic CDH3 variant underlying heredity hypotrichosis simplex detected by whole-exome sequencing (WES)-a case report

Abstract

Heredity hypotrichosis simplex (HHS) is a rare nonsyndromic disease form of hypotrichosis simplex (HS) characterized by progressive hair follicle (HF) miniaturization. It is usually inherited in an autosomal dominant manner. The differential diagnosis of HHS and the treatments remain challenging despite recent advancement. In this report, we describe a 19-yr-old female affected with HHS alongside most of her family members. Whole-exome sequencing (WES) was performed for some of the family members to unravel the culprit gene involved in HHS phenotype and ascertain the dermatological examination that was done to classify the phenotypes of the disease. A novel pathogenic variant in the CDH3 gene (p.Ser223GlyfsTer4) was identified as a plausible disease-causing variant for HHS. This is the first report to associate CDH3 variants with a HHS phenotype without macular degeneration using WES. WES is an important tool for genotype-phenotype correlation, precision in diagnosis, and in-depth understanding of the disease mechanisms, leading to possible novel therapeutic targets treatment and better patient outcomes. copyright