Molecular epidemiology of pachyonychia congenita in the Israeli population.

Pachyonychia congenita (PC) is a rare autosomal dominant disorder featuring palmoplantar keratoderma, nail dystrophy, oral leukokeratosis, pilosebaceous cysts and natal teeth. PC results from dominant mutations in one of five genes encoding keratin proteins including KRT6A, KRT6B, KRT6C, KRT16 or KRT17.We aimed at delineating the clinical and genetic features of PC in a series of Israeli patients.We used direct sequencing of genomic DNA as well as cDNA sequencing when applicable.We collected clinical information and molecular data in a cohort of Israeli families diagnosed with PC (n=16). Most of the patients were Ashkenazi Jews and had a family history of PC. The most common clinical findings were painful focal plantar keratoderma (94%) accompanied by nail dystrophy (81%), pilosebaceous cysts (31%) and prenatal/natal teeth (13%). In contrast to the high prevalence of KRT6A mutations in other populations, KRT16 mutations were most common among Israeli patients with PC (56%). Most (77%) Israeli PC cases with KRT16 mutation carried the same variant (c.380G>A; p.R127H) and shared the same haplotype around the KRT16 locus, suggestive of a founder effect.The data gleaned from this study emphasizes the importance of population-specific tailored diagnostic strategies.

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