A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita

TY - JOUR

T1 - A spectrum of mutations in keratins K6a, K16 and K17 causing pachyonychia congenita

AU - Liao, Haihui

AU - Sayers, Jane M.

AU - Wilson, Neil J.

AU - Irvine, Alan D.

AU - Mellerio, Jemima E.

AU - Baselga, Eulalia

AU - Bayliss, Susan J.

AU - Uliana, Vera

AU - Fimiani, Michele

AU - Lane, E. Birgitte

AU - McLean, W. H. Irwin

AU - Leachman, Sancy A.

AU - Smith, Frances J. D.

PY - 2007/12

Y1 - 2007/12

N2 - Background: Pachyonychia congenita (PC) is a rare autosomal dominant keratin disorder, subdivided into two major variants, PC-1 and PC-2. Predominant characteristics include hypertrophic nail dystrophy, focal palmoplantar keratoderma and oral leukokeratosis. Multiple steatocystomas that develop during puberty are a useful feature distinguishing PC-2 from PC-1. At the molecular level it has been shown that mutations in keratin K6a or K16 cause PC-1 whereas those in K6b or K17 lead to PC-2. Objective: To identify mutations in 22 families presenting with clinical symptoms of either PC-1/focal non-epidermolytic palmoplantar keratoderma (FNEPPK) or PC-2. Methods: Mutation analysis was performed on genomic DNA from PC patients by direct sequencing. Results: Here, we report four new missense and five known mutations in K6a; one new deletion and three previously identified missense mutations in K16; plus one known mutation in K17. Conclusion: With one exception, all these heterozygous mutations are within the highly conserved helix boundary motif regions at either end of the keratin rod domain. In one sporadic case, a unique mutation in K16 resulting in deletion of 24 bp was found within the central rod domain, in a child with a phenotype predominantly consisting of focal plantar keratoderma. The identification of mutations in cases of PC is prerequisite for future development of gene-specific and/or mutation-specific therapies. © 2007 Japanese Society for Investigative Dermatology.

AB - Background: Pachyonychia congenita (PC) is a rare autosomal dominant keratin disorder, subdivided into two major variants, PC-1 and PC-2. Predominant characteristics include hypertrophic nail dystrophy, focal palmoplantar keratoderma and oral leukokeratosis. Multiple steatocystomas that develop during puberty are a useful feature distinguishing PC-2 from PC-1. At the molecular level it has been shown that mutations in keratin K6a or K16 cause PC-1 whereas those in K6b or K17 lead to PC-2. Objective: To identify mutations in 22 families presenting with clinical symptoms of either PC-1/focal non-epidermolytic palmoplantar keratoderma (FNEPPK) or PC-2. Methods: Mutation analysis was performed on genomic DNA from PC patients by direct sequencing. Results: Here, we report four new missense and five known mutations in K6a; one new deletion and three previously identified missense mutations in K16; plus one known mutation in K17. Conclusion: With one exception, all these heterozygous mutations are within the highly conserved helix boundary motif regions at either end of the keratin rod domain. In one sporadic case, a unique mutation in K16 resulting in deletion of 24 bp was found within the central rod domain, in a child with a phenotype predominantly consisting of focal plantar keratoderma. The identification of mutations in cases of PC is prerequisite for future development of gene-specific and/or mutation-specific therapies. © 2007 Japanese Society for Investigative Dermatology.

KW - Gene Deletion

KW - Heterozygote

KW - Humans

KW - Keratin-16

KW - Keratin-17

KW - Keratin-6

KW - Mutation

KW - Mutation, Missense

KW - Pachyonychia Congenita

KW - Sequence Analysis, DNA

U2 - 10.1016/j.jdermsci.2007.07.003

DO - 10.1016/j.jdermsci.2007.07.003

M3 - Article

C2 - 17719747

SN - 0923-1811

VL - 48

SP - 199

EP - 205

JO - Journal of Dermatological Science

JF - Journal of Dermatological Science

IS - 3

ER -