{Reference Type}: Case Reports
{Title}: Palmoplantar keratoderma, oral involvement, and homozygous CTSC mutation in two brothers from Cambodia.
{Author}: Wei H;Wee LWY;Born B;Seang S;Koh MJA;Yee R;Lin G;Rafi'ee K;Mey S;Tan EC;
{Journal}: Am J Med Genet A
{Volume}: 182
{Issue}: 2
{Year}: 02 2020
{Factor}: 2.578
{DOI}: 10.1002/ajmg.a.61447
{Abstract}: 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.