The molecular genetic analysis of the expanding pachyonychia congenita case collection

N. J. Wilson; E. O'Toole; L. M. Milstone; C. D. Hansen; A. A. Shepherd; E. Al-Asadi; M. E. Schwartz; W. H. I. McLean; E. Sprecher; F. J. D. Smith

doi:10.1111/bjd.12958

The molecular genetic analysis of the expanding pachyonychia congenita case collection

N. J. Wilson, E. O'Toole, L. M. Milstone, C. D. Hansen, A. A. Shepherd, E. Al-Asadi, M. E. Schwartz, W. H. I. McLean, E. Sprecher, F. J. D. Smith (Lead / Corresponding author)

Biological Chemistry and Drug Discovery

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Abstract

Background

Pachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma (PPK) and nail dystrophy, often accompanied by oral leukokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes; KRT6A, KRT6B, KRT6C, KRT16 or KRT17.

Objectives

To identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry (IPCRR) during the last few years.

Methods

Genomic DNA isolated from saliva or peripheral blood leukocytes was amplified using primers specific for the PC associated keratin genes and PCR products were directly sequenced.

Results

Mutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105.

Conclusions

This study has confirmed at the molecular level the clinical diagnosis of PC in these families, by identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17.

Original language	English
Article number	12958
Pages (from-to)	343-355
Number of pages	13
Journal	British Journal of Dermatology
Volume	171
Issue number	2
Early online date	10 Mar 2014
DOIs	https://doi.org/10.1111/bjd.12958
Publication status	Published - Aug 2014

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10.1111/bjd.12958Licence: CC BY

Publisher final version
© 2014 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Attribution — You must give appropriate credit, provide a link to the license, andindicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
Final published version, 1.01 MBLicence: CC BY

Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)
Barton, G. (Investigator), Campbell, P. (Investigator), Hickerson, R. (Investigator), Leigh, I. (Investigator), McLean, I. (Investigator) & Wyatt, P. (Investigator)
1/08/12 → 30/04/19
Project: Research

Cite this

@article{edf4b56208294c569350443df6e69cd9,

title = "The molecular genetic analysis of the expanding pachyonychia congenita case collection",

abstract = "BackgroundPachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma (PPK) and nail dystrophy, often accompanied by oral leukokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes; KRT6A, KRT6B, KRT6C, KRT16 or KRT17.ObjectivesTo identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry (IPCRR) during the last few years.MethodsGenomic DNA isolated from saliva or peripheral blood leukocytes was amplified using primers specific for the PC associated keratin genes and PCR products were directly sequenced.ResultsMutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105.ConclusionsThis study has confirmed at the molecular level the clinical diagnosis of PC in these families, by identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17.",

author = "Wilson, {N. J.} and E. O'Toole and Milstone, {L. M.} and Hansen, {C. D.} and Shepherd, {A. A.} and E. Al-Asadi and Schwartz, {M. E.} and McLean, {W. H. I.} and E. Sprecher and Smith, {F. J. D.}",

note = "These articles have been accepted for publication in the British Journal of Dermatology and are currently being edited and typeset. Readers should note that articles published below have been fully refereed, but have not been through the copy-editing and proof correction process. Wiley-Blackwell and the British Association of Dermatologists cannot be held responsible for errors or consequences arising from the use of information contained in these articles; nor do the views and opinions expressed necessarily reflect those of Wiley-Blackwell or the British Association of Dermatologists. This article is protected by copyright. All rights reserved.",

year = "2014",

month = aug,

doi = "10.1111/bjd.12958",

language = "English",

volume = "171",

pages = "343--355",

journal = "British Journal of Dermatology",

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T1 - The molecular genetic analysis of the expanding pachyonychia congenita case collection

AU - Wilson, N. J.

AU - O'Toole, E.

AU - Milstone, L. M.

AU - Hansen, C. D.

AU - Shepherd, A. A.

AU - Al-Asadi, E.

AU - Schwartz, M. E.

AU - McLean, W. H. I.

AU - Sprecher, E.

AU - Smith, F. J. D.

N1 - These articles have been accepted for publication in the British Journal of Dermatology and are currently being edited and typeset. Readers should note that articles published below have been fully refereed, but have not been through the copy-editing and proof correction process. Wiley-Blackwell and the British Association of Dermatologists cannot be held responsible for errors or consequences arising from the use of information contained in these articles; nor do the views and opinions expressed necessarily reflect those of Wiley-Blackwell or the British Association of Dermatologists. This article is protected by copyright. All rights reserved.

PY - 2014/8

Y1 - 2014/8

N2 - BackgroundPachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma (PPK) and nail dystrophy, often accompanied by oral leukokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes; KRT6A, KRT6B, KRT6C, KRT16 or KRT17.ObjectivesTo identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry (IPCRR) during the last few years.MethodsGenomic DNA isolated from saliva or peripheral blood leukocytes was amplified using primers specific for the PC associated keratin genes and PCR products were directly sequenced.ResultsMutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105.ConclusionsThis study has confirmed at the molecular level the clinical diagnosis of PC in these families, by identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17.

AB - BackgroundPachyonychia congenita (PC) is a rare autosomal dominant keratinizing disorder characterized by severe, painful, palmoplantar keratoderma (PPK) and nail dystrophy, often accompanied by oral leukokeratosis, cysts and follicular keratosis. It is caused by mutations in one of five keratin genes; KRT6A, KRT6B, KRT6C, KRT16 or KRT17.ObjectivesTo identify mutations in 84 new families with a clinical diagnosis of PC, recruited by the International Pachyonychia Congenita Research Registry (IPCRR) during the last few years.MethodsGenomic DNA isolated from saliva or peripheral blood leukocytes was amplified using primers specific for the PC associated keratin genes and PCR products were directly sequenced.ResultsMutations were identified in 84 families in the PC-associated keratin genes, comprising 46 distinct keratin mutations. Fourteen were previously unreported mutations, bringing the total number of different keratin mutations associated with PC to 105.ConclusionsThis study has confirmed at the molecular level the clinical diagnosis of PC in these families, by identifying mutations in KRT6A, KRT6B, KRT6C, KRT16 or KRT17.

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DO - 10.1111/bjd.12958

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VL - 171

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EP - 355

JO - British Journal of Dermatology

JF - British Journal of Dermatology

IS - 2

M1 - 12958

ER -

The molecular genetic analysis of the expanding pachyonychia congenita case collection

Abstract

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Projects

Dermatology and Genetic Medicine (Strategic Grant) (Joint with Kings College London)

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