Mutation p.Leu128Pro in the 1A domain of K16 causes pachyonychia congenita with focal palmoplantar keratoderma in a Chinese family

European Journal of Pediatrics
Limeng DaiQiong Liao

Abstract

Pachyonychia congenita (PC), a rare autosomal dominant disorder characterized by hypertrophic nail dystrophy, is classified into two main clinical subtypes: PC-1 and PC-2. PC-1 is associated with mutations in the KRT6A or KRT16 genes, whereas PC-2 is linked to KRT6B or KRT17 mutations. Blood samples were collected from three generations of a new Chinese PC-1 family, including three PC patients and five unaffected family members. A novel missense mutation p.Leu128Pro (c.383T>C) was identified in a highly conserved helix motif in domain 1A of K16. The disease haplotype carried the mutation and cosegregated with the affection status. PolyPhen2 and SIFTS analysis rated the substitution as probably damaging; Swiss-Model analysis indicated that the structure of the mutant protein contained an unnormal α-helix. Overexpression of mutant protein in cultured cells led to abnormal cell morphology. The wider spectrum of KRT16 mutations suggests that changes in codons 125, 127, and 132 are most commonly responsible for PC-1 and that proline substitution mutations at codons 127 or 128 may produce more severe disease. This study extends the KRT16 mutation spectrum and adds new information on the clinical and genetic diversity of PC.

References

Mar 1, 1995·Nature Genetics·W H McLeanC Higgins
Jul 1, 1995·Nature Genetics·P E BowdenR J Turner
Mar 12, 2002·The Journal of Investigative Dermatology·A TerrinoniW H McLean
Nov 26, 2002·The Journal of Investigative Dermatology·Kelsie M BernotKevin M McGowan
Oct 28, 2005·The Journal of Investigative Dermatology. Symposium Proceedings·Sancy A LeachmanE Birgitte Lane
Oct 28, 2005·The Journal of Investigative Dermatology. Symposium Proceedings·Frances J D SmithW H Irwin McLean
Nov 23, 2005·Bioinformatics·Konstantin ArnoldTorsten Schwede
Aug 28, 2007·Journal of Dermatological Science·Haihui LiaoFrances J D Smith
Dec 17, 2010·The Journal of Investigative Dermatology·Teresa FuJean Y Tang
Feb 18, 2011·The Journal of Investigative Dermatology·Neil J WilsonFrances J D Smith
Mar 18, 2011·Human Mutation·Janita ThusbergMauno Vihinen
Mar 25, 2011·The Journal of Investigative Dermatology·W H Irwin McLeanFrances J D Smith
Aug 2, 2011·The British Journal of Dermatology·E AkasakaD Sawamura
Feb 18, 2012·The Journal of Investigative Dermatology·Juliane C Lessard, Pierre A Coulombe

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