Journal home
Advance online publication
Current issue
Archive
Press releases
Free Association (blog)
Supplements
Focuses
Guide to authors
Online submissionOnline submission
For referees
Free online issue
Contact the journal
Subscribe
Advertising
work@npg
Reprints and permissions
About this site
For librarians
 
NPG Resources
Nature
Nature Biotechnology
Nature Cell Biology
Nature Medicine
Nature Methods
Nature Reviews Cancer
Nature Reviews Genetics
Nature Reviews Molecular Cell Biology
news@nature.com
Nature Conferences
RNAi Gateway
NPG Subject areas
Biotechnology
Cancer
Chemistry
Clinical Medicine
Dentistry
Development
Drug Discovery
Earth Sciences
Evolution & Ecology
Genetics
Immunology
Materials Science
Medical Research
Microbiology
Molecular Cell Biology
Neuroscience
Pharmacology
Physics
Browse all publications
Letter
Nature Genetics 38, 337 - 342 (2006)
Published online: 29 January 2006; | doi:10.1038/ng1743

Loss-of-function mutations in the gene encoding filaggrin cause ichthyosis vulgaris

Frances J D Smith1, Alan D Irvine2, Ana Terron-Kwiatkowski1, Aileen Sandilands1, Linda E Campbell1, Yiwei Zhao1, Haihui Liao1, Alan T Evans3, David R Goudie4, Sue Lewis-Jones5, Gehan Arseculeratne5, Colin S Munro6, Ann Sergeant6, Gráinne O'Regan2, Sherri J Bale7, John G Compton7, John J DiGiovanna8, 9, Richard B Presland10, 11, Philip Fleckman11 & W H Irwin McLean1

1  Epithelial Genetics Group, Human Genetics Unit, Division of Pathology and Neuroscience, University of Dundee, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK.

2  Department of Paediatric Dermatology, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.

3  Pathology, Tayside University Hospitals NHS Trust, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK.

4  Clinical Genetics, Tayside University Hospitals NHS Trust, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK.

5  Dermatology, Tayside University Hospitals NHS Trust, Ninewells Hospital & Medical School, Dundee DD1 9SY, UK.

6  Department of Dermatology, South Glasgow University Hospitals NHS Trust, Glasgow, G51 4TF, UK.

7  Gene Dx, Gaithersburg, Maryland 20877, USA.

8  Division of Dermatopharmacology, Department of Dermatology, Brown Medical School and Rhode Island Hospital, Providence, Rhode Island 02903, USA.

9  Basic Research Laboratory, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.

10  Oral Biology, School of Dentistry, University of Washington, Seattle, Washington 98195, USA.

11  Division of Dermatology, Department of Medicine, University of Washington, Seattle, Washington 98195, USA.

Correspondence should be addressed to W H Irwin McLean w.h.i.mclean@dundee.ac.uk

Ichthyosis vulgaris (OMIM 146700) is the most common inherited disorder of keratinization and one of the most frequent single-gene disorders in humans. The most widely cited incidence figure is 1 in 250 based on a survey of 6,051 healthy English schoolchildren1. We have identified homozygous or compound heterozygous mutations R501X and 2282del4 in the gene encoding filaggrin (FLG) as the cause of moderate or severe ichthyosis vulgaris in 15 kindreds. In addition, these mutations are semidominant; heterozygotes show a very mild phenotype with incomplete penetrance. The mutations show a combined allele frequency of approx4% in populations of European ancestry, explaining the high incidence of ichthyosis vulgaris. Profilaggrin is the major protein of keratohyalin granules in the epidermis. During terminal differentiation, it is cleaved into multiple filaggrin peptides that aggregate keratin filaments. The resultant matrix is cross-linked to form a major component of the cornified cell envelope. We find that loss or reduction of this major structural protein leads to varying degrees of impaired keratinization.


MORE ARTICLES LIKE THIS

These links to content published by NPG are automatically generated.

NEWS AND VIEWS

Skin barrier function and allergic risk

Nature Genetics News and Views (01 Apr 2006)

Of flaky tails and itchy skin

Nature Genetics News and Views (01 May 2009)

 Top
Abstract
Previous | Next
Table of contents
Full textFull text
Download PDFDownload PDF
Send to a friendSend to a friend
rights and permissionsRights and permissions
CrossRef lists 455 articles citing this articleCrossRef lists 455 articles citing this article
Save this linkSave this link
Figures & Tables
Supplementary info
Export citation

natureevents

natureproducts

Search buyers guide:

 
Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
Journal home | Advance online publication | Current issue | Archive | Press releases | Supplements | Focuses | For authors | Online submission | Permissions | For referees | Free online issue | About the journal | Contact the journal | Subscribe | Advertising | work@npg | naturereprints | About this site | For librarians
Nature Publishing Group, publisher of Nature, and other science journals and reference works©2006 Nature Publishing Group | Privacy policy