Background: Epidermolytic palmoplantar keratoderma (EPPK) is a rare skin disorder and its pathogenesis and inheritability are unknown.
Objective: To investigate the inheritance and pathogenesis of EPPK.
Methods: Two EPPK cases occurred in a three-generation Chinese family. Patient-parents trio EPPK was carried out and the identified candidate variants were confirmed by Sanger sequencing.
Results: A heterozygous missense pathogenic variant, c.488G > A (p.Arg163Gln), in the keratin (KRT) 9 gene was detected in the proband and his son via targeted exome sequencing, and then validated by Sanger sequencing. This pathogenic variant cosegregated with the EPPK in extended family members, and was predicted to be pathogenic by SIFT, PolyPhen2, PROVEAN, and Mutation Taster. This heterozygous variation was not evident in 100 healthy controls.
Conclusion: This report describes a KRT9 c.488G > A (p.Arg163Gln) variant causing a diffuse phenotype of Chinese EPPK. The current results broaden the spectrum of KRT9 pathogenic variants responsible for EPPK and have important implications for molecular diagnosis, treatment, and genetic counseling for this family.
Keywords: Keratin 9; epidermolytic palmoplantar keratoderma; exome sequencing.
© 2019 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.