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Palmoplantar keratoderma, oral involvement, and homozygous CTSC mutation in two brothers from Cambodia
Author(s) -
Wei Heming,
Wee Lynette W. Y.,
Born Bori,
Seang Sokheng,
Koh Mark J. A.,
Yee Ruixiang,
Lin Grace,
Rafi'ee Khadijah,
Mey Sithach,
Tan EneChoo
Publication year - 2020
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61447
Subject(s) - palmoplantar keratoderma , compound heterozygosity , genodermatosis , missense mutation , cathepsin c , periodontitis , medicine , genetics , mutation , dermatology , pathology , hyperkeratosis , biology , gene , cathepsin , biochemistry , enzyme
Haim–Munk syndrome (HMS) and Papillon–Lefevre syndrome (PLS) are phenotypic variants of palmoplantar keratoderma (PPK) with progressive early‐onset periodontitis and dental caries. HMS and PLS have been associated with homozygous or compound heterozygous mutations in the lysosomal protease gene Cathepsin C ( CTSC ). There have been only a few documented cases of CTSC mutations in patients from South‐East Asia. We report the clinical findings of two Cambodian brothers who presented with diffuse, demarcated PPK with transgrediens extending to the elbows and knees, as well as pachyonychia and dental caries. Arachnodactyly and periodontitis were also found in the older brother. Next‐generation sequencing unveiled a homozygous missense variant in CTSC (NM_001814.5: c.1337AC: p.(Asp446Ala)) in both brothers. Both parents were heterozygous for the variant, while an unaffected older brother was homozygous for the wild‐type allele. Our study adds to the spectrum of mutations and associated clinical presentations for this rare genodermatosis.