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Haploinsufficiency of Desmoplakin Causes a Striate Subtype of Palmoplantar Keratoderma

Haploinsufficiency of Desmoplakin Causes a Striate Subtype of Palmoplantar Keratoderma Desmosomes are highly organized intercellular adhesive junctions that are particularly prominent in epidermis and other tissues experiencing mechanical stress. Desmoplakin, a constitutive component of the desmosomal plaque, is the most abundant protein present in such junctions and plays a critical role in linking the intermediate filament network to the plasma membrane in these tissues. Here we report the first mutation in the gene encoding desmoplakin. The identified mutation, resulting in a null allele and haploinsufficiency, was observed in genomic DNA from a kindred with the dominantly inherited skin disorder, striate palmoplantar keratoderma. Affected individuals had a linear pattern of skin thickening on the fingers and palms and circumscribed areas of skin thickening on the soles. Affected skin demonstrated loosening of intercellular connections, disruption of desmosomekeratin intermediate filament interactions and a proportion of rudimentary desmosomal structures. The disorder mapped to chromosome 6p21 with a maximum lod score of 10.67. The mutation was a heterozygous C→T transition in exon 4 of the desmoplakin gene and predicted a premature termination codon in the N-terminal region of the peptide. This is the first reported mutation of desmoplakin and also the first inherited skin disorder in which haploinsufficiency of a structural component has been implicated. It identifies dosage of desmoplakin as critical in maintaining epidermal integrity. © 1999 Oxford University Press « Previous | Next Article » Table of Contents This Article Hum. Mol. Genet. (1999) 8 (1): 143-148. doi: 10.1093/hmg/8.1.143 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free A correction has been published Classifications Article Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Armstrong, D. K. B. Articles by Hughes, A. E. Search for related content PubMed PubMed citation Articles by Armstrong, D. K. B. Articles by McKenna, K. E. Articles by Purkis, P. E. Articles by Green, K. J. Articles by Eady, R. A. J. Articles by Leigh, I. M. Articles by Hughes, A. E. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue November 15, 2015 24 (22) Alert me to new issues The Journal About this journal Rights & Permissions Dispatch date of the next issue This journal is a member of the Committee on Publication Ethics (COPE) We are mobile – find out more Journals Career Network Impact factor: 6.393 5-Yr impact factor: 6.850 Executive Editors Professor Kay Davies Professor Anthony Wynshaw-Boris Professor Joel Hirschhorn Dr Jeffrey Barrett View full editorial board For Authors Instructions to authors Online submission Submit Now! Self-archiving policy Open access options for authors - visit Oxford Open This journal enables compliance with the NIH Public Access Policy Alerting Services Email table of contents Email Advance Access CiteTrack XML RSS feed Corporate Services Advertising sales Reprints Supplements var taxonomies = ("SCI01140"); Most Most Read Genetics of obesity and the prediction of risk for health Non-coding RNA Telomerase and cancer Ion channel diseases Down syndrome--recent progress and future prospects » View all Most Read articles Most Cited The DNA methyltransferases of mammals Nonsense-Mediated mRNA Decay in Health and Disease Mutation of human short tandem repeats Prediction of deleterious human alleles Isolation of a Candidate Human Telomerase Catalytic Subunit Gene, Which Reveals Complex Splicing Patterns in Different Cell Types » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. 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Haploinsufficiency of Desmoplakin Causes a Striate Subtype of Palmoplantar Keratoderma

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Publisher
Oxford University Press
Copyright
Copyright © 2015 Oxford University Press
ISSN
0964-6906
eISSN
1460-2083
DOI
10.1093/hmg/8.1.143
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Abstract

Desmosomes are highly organized intercellular adhesive junctions that are particularly prominent in epidermis and other tissues experiencing mechanical stress. Desmoplakin, a constitutive component of the desmosomal plaque, is the most abundant protein present in such junctions and plays a critical role in linking the intermediate filament network to the plasma membrane in these tissues. Here we report the first mutation in the gene encoding desmoplakin. The identified mutation, resulting in a null allele and haploinsufficiency, was observed in genomic DNA from a kindred with the dominantly inherited skin disorder, striate palmoplantar keratoderma. Affected individuals had a linear pattern of skin thickening on the fingers and palms and circumscribed areas of skin thickening on the soles. Affected skin demonstrated loosening of intercellular connections, disruption of desmosomekeratin intermediate filament interactions and a proportion of rudimentary desmosomal structures. The disorder mapped to chromosome 6p21 with a maximum lod score of 10.67. The mutation was a heterozygous C→T transition in exon 4 of the desmoplakin gene and predicted a premature termination codon in the N-terminal region of the peptide. This is the first reported mutation of desmoplakin and also the first inherited skin disorder in which haploinsufficiency of a structural component has been implicated. It identifies dosage of desmoplakin as critical in maintaining epidermal integrity. © 1999 Oxford University Press « Previous | Next Article » Table of Contents This Article Hum. Mol. Genet. (1999) 8 (1): 143-148. doi: 10.1093/hmg/8.1.143 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free A correction has been published Classifications Article Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Citing articles via Google Scholar Google Scholar Articles by Armstrong, D. K. B. Articles by Hughes, A. E. Search for related content PubMed PubMed citation Articles by Armstrong, D. K. B. Articles by McKenna, K. E. Articles by Purkis, P. E. Articles by Green, K. J. Articles by Eady, R. A. J. Articles by Leigh, I. M. Articles by Hughes, A. E. Related Content Load related web page information Share Email this article CiteULike Delicious Facebook Google+ Mendeley Twitter What's this? Search this journal: Advanced » Current Issue November 15, 2015 24 (22) Alert me to new issues The Journal About this journal Rights & Permissions Dispatch date of the next issue This journal is a member of the Committee on Publication Ethics (COPE) We are mobile – find out more Journals Career Network Impact factor: 6.393 5-Yr impact factor: 6.850 Executive Editors Professor Kay Davies Professor Anthony Wynshaw-Boris Professor Joel Hirschhorn Dr Jeffrey Barrett View full editorial board For Authors Instructions to authors Online submission Submit Now! Self-archiving policy Open access options for authors - visit Oxford Open This journal enables compliance with the NIH Public Access Policy Alerting Services Email table of contents Email Advance Access CiteTrack XML RSS feed Corporate Services Advertising sales Reprints Supplements var taxonomies = ("SCI01140"); Most Most Read Genetics of obesity and the prediction of risk for health Non-coding RNA Telomerase and cancer Ion channel diseases Down syndrome--recent progress and future prospects » View all Most Read articles Most Cited The DNA methyltransferases of mammals Nonsense-Mediated mRNA Decay in Health and Disease Mutation of human short tandem repeats Prediction of deleterious human alleles Isolation of a Candidate Human Telomerase Catalytic Subunit Gene, Which Reveals Complex Splicing Patterns in Different Cell Types » View all Most Cited articles Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department. Online ISSN 1460-2083 - Print ISSN 0964-6906 Copyright © 2015 Oxford University Press Oxford Journals Oxford University Press Site Map Privacy Policy Cookie Policy Legal Notices Frequently Asked Questions Other Oxford University Press sites: Oxford University Press Oxford Journals China Oxford Journals Japan Academic & Professional books Children's & Schools Books Dictionaries & Reference Dictionary of National Biography Digital Reference English Language Teaching Higher Education Textbooks International Education Unit Law Medicine Music Online Products & Publishing Oxford Bibliographies Online Oxford Dictionaries Online Oxford English Dictionary Oxford Language Dictionaries Online Oxford Scholarship Online Reference Rights and Permissions Resources for Retailers & Wholesalers Resources for the Healthcare Industry Very Short Introductions World's Classics function fnc_onDomLoaded() { var query_context = getQueryContext(); PF_initOIUnderbar(query_context,":QS:default","","JRN"); PF_insertOIUnderbar(0); }; if (window.addEventListener) { window.addEventListener('load', fnc_onDomLoaded, false); } else if (window.attachEvent) { window.attachEvent('onload', fnc_onDomLoaded); } var gaJsHost = (("https:" == document.location.protocol) ? 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Journal

Human Molecular Genetics – Oxford University Press

Published: Jan 1, 1999

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