Mutations in desmoglein-1 cause diverse inherited palmoplantar keratoderma phenotypes

implications for genetic screening

M.-L. Lovgren (Lead / Corresponding author), M. A. McAleer, A. D. Irvine, N. J. Wilson, S. Tavadia, M. E. Schwartz, C. Cole, A. Sandilands, F. J. D. Smith, M. Zamiri

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Abstract

INTRODUCTION: The inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of genodermatoses, characterised by thickening of the epidermis of the palms and soles. No classification system unites satisfactorily clinical presentation, pathology and molecular pathogenesis. There are four patterns of hyperkeratosis: striate, focal, diffuse, and punctate. Mutations in desmoglein-1 (DSG1), a transmembrane glycoprotein, have been reported primarily in striate, but also in focal and diffuse PPKs.

OBJECTIVES: We report seven unrelated pedigrees with dominantly inherited PPK due to mutations in the DSG1 gene, with marked phenotypic variation.

METHODS: Genomic DNA from each family was isolated, and individual exons amplified by polymerase chain reaction (PCR). Sanger sequencing was employed to identify mutations.

RESULTS: Mutation analysis identified novel mutations in five families (p.Tyr126Hisfs*2, p.Ser521Tyrfs*2, p.Trp3*, p.Asp591Phefs*9 and p.Met249Ilefs*6) with striate palmar involvement and varying focal or diffuse plantar disease, and the recurrent mutation c.76C>T, p.Arg26*, in two families with variable PPK patterns.

CONCLUSION: We report one recurrent and five novel DSG1 mutations, causing varying patterns of PPK, highlighting the clinical heterogeneity arising from mutations in this gene. This article is protected by copyright. All rights reserved.

Original languageEnglish
JournalBritish Journal of Dermatology
Early online date18 Aug 2016
DOIs
Publication statusPublished - 2 Apr 2017

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Desmoglein 1
Palmoplantar Keratoderma
Genetic Testing
Phenotype
Mutation
Clinical Pathology
Pedigree
Epidermis
Genes
Exons
Glycoproteins
Polymerase Chain Reaction

Cite this

@article{0ee9f85369f04d7aa1962ff51466df7d,
title = "Mutations in desmoglein-1 cause diverse inherited palmoplantar keratoderma phenotypes: implications for genetic screening",
abstract = "INTRODUCTION: The inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of genodermatoses, characterised by thickening of the epidermis of the palms and soles. No classification system unites satisfactorily clinical presentation, pathology and molecular pathogenesis. There are four patterns of hyperkeratosis: striate, focal, diffuse, and punctate. Mutations in desmoglein-1 (DSG1), a transmembrane glycoprotein, have been reported primarily in striate, but also in focal and diffuse PPKs.OBJECTIVES: We report seven unrelated pedigrees with dominantly inherited PPK due to mutations in the DSG1 gene, with marked phenotypic variation.METHODS: Genomic DNA from each family was isolated, and individual exons amplified by polymerase chain reaction (PCR). Sanger sequencing was employed to identify mutations.RESULTS: Mutation analysis identified novel mutations in five families (p.Tyr126Hisfs*2, p.Ser521Tyrfs*2, p.Trp3*, p.Asp591Phefs*9 and p.Met249Ilefs*6) with striate palmar involvement and varying focal or diffuse plantar disease, and the recurrent mutation c.76C>T, p.Arg26*, in two families with variable PPK patterns.CONCLUSION: We report one recurrent and five novel DSG1 mutations, causing varying patterns of PPK, highlighting the clinical heterogeneity arising from mutations in this gene. This article is protected by copyright. All rights reserved.",
author = "M.-L. Lovgren and McAleer, {M. A.} and Irvine, {A. D.} and Wilson, {N. J.} and S. Tavadia and Schwartz, {M. E.} and C. Cole and A. Sandilands and Smith, {F. J. D.} and M. Zamiri",
note = "F.J.D.S. and N.J.W. were supported by grants from the Pachyonychia Congenita Project (to F.J.D.S., www.pachyonychia.org). The Centre for Dermatology and Genetic Medicine at the University of Dundee is supported by a Wellcome Trust Strategic Award (098439/Z/12/Z).",
year = "2017",
month = "4",
day = "2",
doi = "10.1111/bjd.14973",
language = "English",
journal = "British Journal of Dermatology",
issn = "0007-0963",
publisher = "Wiley",

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Mutations in desmoglein-1 cause diverse inherited palmoplantar keratoderma phenotypes : implications for genetic screening. / Lovgren, M.-L. (Lead / Corresponding author); McAleer, M. A.; Irvine, A. D.; Wilson, N. J.; Tavadia, S.; Schwartz, M. E.; Cole, C.; Sandilands, A.; Smith, F. J. D.; Zamiri, M.

In: British Journal of Dermatology, 02.04.2017.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mutations in desmoglein-1 cause diverse inherited palmoplantar keratoderma phenotypes

T2 - implications for genetic screening

AU - Lovgren, M.-L.

AU - McAleer, M. A.

AU - Irvine, A. D.

AU - Wilson, N. J.

AU - Tavadia, S.

AU - Schwartz, M. E.

AU - Cole, C.

AU - Sandilands, A.

AU - Smith, F. J. D.

AU - Zamiri, M.

N1 - F.J.D.S. and N.J.W. were supported by grants from the Pachyonychia Congenita Project (to F.J.D.S., www.pachyonychia.org). The Centre for Dermatology and Genetic Medicine at the University of Dundee is supported by a Wellcome Trust Strategic Award (098439/Z/12/Z).

PY - 2017/4/2

Y1 - 2017/4/2

N2 - INTRODUCTION: The inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of genodermatoses, characterised by thickening of the epidermis of the palms and soles. No classification system unites satisfactorily clinical presentation, pathology and molecular pathogenesis. There are four patterns of hyperkeratosis: striate, focal, diffuse, and punctate. Mutations in desmoglein-1 (DSG1), a transmembrane glycoprotein, have been reported primarily in striate, but also in focal and diffuse PPKs.OBJECTIVES: We report seven unrelated pedigrees with dominantly inherited PPK due to mutations in the DSG1 gene, with marked phenotypic variation.METHODS: Genomic DNA from each family was isolated, and individual exons amplified by polymerase chain reaction (PCR). Sanger sequencing was employed to identify mutations.RESULTS: Mutation analysis identified novel mutations in five families (p.Tyr126Hisfs*2, p.Ser521Tyrfs*2, p.Trp3*, p.Asp591Phefs*9 and p.Met249Ilefs*6) with striate palmar involvement and varying focal or diffuse plantar disease, and the recurrent mutation c.76C>T, p.Arg26*, in two families with variable PPK patterns.CONCLUSION: We report one recurrent and five novel DSG1 mutations, causing varying patterns of PPK, highlighting the clinical heterogeneity arising from mutations in this gene. This article is protected by copyright. All rights reserved.

AB - INTRODUCTION: The inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of genodermatoses, characterised by thickening of the epidermis of the palms and soles. No classification system unites satisfactorily clinical presentation, pathology and molecular pathogenesis. There are four patterns of hyperkeratosis: striate, focal, diffuse, and punctate. Mutations in desmoglein-1 (DSG1), a transmembrane glycoprotein, have been reported primarily in striate, but also in focal and diffuse PPKs.OBJECTIVES: We report seven unrelated pedigrees with dominantly inherited PPK due to mutations in the DSG1 gene, with marked phenotypic variation.METHODS: Genomic DNA from each family was isolated, and individual exons amplified by polymerase chain reaction (PCR). Sanger sequencing was employed to identify mutations.RESULTS: Mutation analysis identified novel mutations in five families (p.Tyr126Hisfs*2, p.Ser521Tyrfs*2, p.Trp3*, p.Asp591Phefs*9 and p.Met249Ilefs*6) with striate palmar involvement and varying focal or diffuse plantar disease, and the recurrent mutation c.76C>T, p.Arg26*, in two families with variable PPK patterns.CONCLUSION: We report one recurrent and five novel DSG1 mutations, causing varying patterns of PPK, highlighting the clinical heterogeneity arising from mutations in this gene. This article is protected by copyright. All rights reserved.

U2 - 10.1111/bjd.14973

DO - 10.1111/bjd.14973

M3 - Article

JO - British Journal of Dermatology

JF - British Journal of Dermatology

SN - 0007-0963

ER -