A large mutational study in pachyonychia congenita.

Article Details

Citation

Wilson NJ, Leachman SA, Hansen CD, McMullan AC, Milstone LM, Schwartz ME, McLean WH, Hull PR, Smith FJ

A large mutational study in pachyonychia congenita.

J Invest Dermatol. 2011 May;131(5):1018-24. doi: 10.1038/jid.2011.20. Epub 2011 Feb 17.

PubMed ID
21326300 [ View in PubMed
]
Abstract

Pachyonychia congenita (PC) is a rare autosomal dominant skin disorder characterized predominantly by nail dystrophy and painful palmoplantar keratoderma. Additional clinical features include oral leukokeratosis, follicular keratosis, and cysts (steatocysts and pilosebaceous cysts). PC is due to heterozygous mutations in one of four keratin genes, namely, KRT6A, KRT6B, KRT16, or KRT17. Here, we report genetic analysis of 90 new families with PC in which we identified mutations in KRT6A, KRT6B, KRT16, or KRT17, thereby confirming their clinical diagnosis. A total of 21 previously unreported and 22 known mutations were found. Approximately half of the kindreds had mutations in KRT6A (52%), 28% had mutations in KRT16, 17% in KRT17, and 3% of families had mutations in KRT6B. Most of the mutations were heterozygous missense or small in-frame insertion/deletion mutations occurring within one of the helix boundary motif regions of the keratin polypeptide. More unusual mutations included heterozygous splice site mutations, nonsense mutations, and a 1-bp insertion mutation, leading to a frameshift and premature termination codon. This study, together with previously reported mutations, identifies mutation hotspot codons that may be useful in the development of personalized medicine for PC.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Keratin, type I cytoskeletal 16P08779Details
Keratin, type II cytoskeletal 6AP02538Details