TY - JOUR
T1 - Keratin K6c mutations cause focal palmoplantar keratoderma
AU - Wilson, Neil J.
AU - Messenger, Andrew G.
AU - Leachman, Sancy A.
AU - O'Toole, Edel A.
AU - Lane, E. Birgitte
AU - McLean, W. H.Irwin
AU - Smith, Frances J.D.
N1 - Funding Information:
We thank the patients and Dr Ian Pearson, Royal Bournemouth and Christchurch Hospital, UK, for their participation in this research. This research was supported by grants to F.J.D.S., W.H.I.M. and E.B.L. from the Pachyonychia Congenita Project and the Dystrophic Epidermolysis Bullosa Research Association UK (DEBRA UK).
PY - 2010/2
Y1 - 2010/2
N2 - The palmoplantar keratodermas (PPKs) are a large group of clinically and genetically heterogeneous genodermatoses. The gene defects underlying many PPKs still need to be resolved to facilitate definitive molecular diagnosis and genetic counseling. Dominant-negative mutations in any of the four identified keratin genes, KRT6A, KRT6B, KRT16, or KRT17, cause pachyonychia congenita (PC), characterized by hypertrophic nail dystrophy and other ectodermal features. In PC, focal PPK (FPPK) is the most painful and debilitating phenotypic feature. Some families presenting with FPPK alone, or with minimal nail changes, carry mutations in KRT16; however, most FPPK families do not harbor mutations in any of these keratin genes. Here, we report three unrelated families who presented with familial FPPK with minor or absent nail changes. The four PC/FPPK-related keratin genes were excluded; however, mutational analysis of the recently identified KRT6C gene, encoding keratin K6c, showed heterozygous in-frame deletion mutations in all three kindreds. Affected members of Families 1 and 2 carried the same mutation, p.Asn172del. In Family 3, the mutation p.Ile462-Glu470del co-segregated with the disease. KRT6C was shown to be expressed in the plantar epidermis using reverse transcription-PCR, consistent with the phenotype observed in this tissue. These data expand the genetic testing repertoire for the PPKs.
AB - The palmoplantar keratodermas (PPKs) are a large group of clinically and genetically heterogeneous genodermatoses. The gene defects underlying many PPKs still need to be resolved to facilitate definitive molecular diagnosis and genetic counseling. Dominant-negative mutations in any of the four identified keratin genes, KRT6A, KRT6B, KRT16, or KRT17, cause pachyonychia congenita (PC), characterized by hypertrophic nail dystrophy and other ectodermal features. In PC, focal PPK (FPPK) is the most painful and debilitating phenotypic feature. Some families presenting with FPPK alone, or with minimal nail changes, carry mutations in KRT16; however, most FPPK families do not harbor mutations in any of these keratin genes. Here, we report three unrelated families who presented with familial FPPK with minor or absent nail changes. The four PC/FPPK-related keratin genes were excluded; however, mutational analysis of the recently identified KRT6C gene, encoding keratin K6c, showed heterozygous in-frame deletion mutations in all three kindreds. Affected members of Families 1 and 2 carried the same mutation, p.Asn172del. In Family 3, the mutation p.Ile462-Glu470del co-segregated with the disease. KRT6C was shown to be expressed in the plantar epidermis using reverse transcription-PCR, consistent with the phenotype observed in this tissue. These data expand the genetic testing repertoire for the PPKs.
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U2 - 10.1038/jid.2009.215
DO - 10.1038/jid.2009.215
M3 - Article
C2 - 19609311
AN - SCOPUS:75549091026
SN - 0022-202X
VL - 130
SP - 425
EP - 429
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 2
ER -