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Multiple self-healing squamous epithelioma is caused by a disease-specific spectrum of mutations in TGFBR1

Research output: Contribution to journalArticle

David R. Goudie, Mariella D'Alessandro, Barry Merriman, Hane Lee, Ildiko Szeverenyi, Stuart Avery, Brian D. O'Connor, Stanley F. Nelson, Stephanie E. Coats, Arlene Stewart, Lesley Christie, Gabriella Pichert, Jean Friedel, Ian Hayes, Nigel Burrows, Sean Whittaker, Anne-Marie Gerdes, Sigurd Broesby-Olsen, Malcolm A. Ferguson-Smith, Chandra Verma & 3 more Declan P. Lunny, Bruno Reversade, E. Birgitte Lane

Original languageEnglish
Pages (from-to)365 - U121
Number of pages7
JournalNature Genetics
Volume43
Issue number4
DOIs
Publication statusPublished - Feb 2011

King's Authors

Abstract

Multiple self-healing squamous epithelioma (MSSE), also known as Ferguson-Smith disease (FSD), is an autosomal-dominant skin cancer condition characterized by multiple squamous-carcinoma-like locally invasive skin tumors that grow rapidly for a few weeks before spontaneously regressing, leaving scars(1,2). High-throughput genomic sequencing of a conservative estimate (24.2 Mb) of the disease locus on chromosome 9 using exon array capture identified independent mutations in TGFBR1 in three unrelated families. Subsequent dideoxy sequencing of TGFBR1 identified 11 distinct monoallelic mutations in 18 affected families, firmly establishing TGFBR1 as the causative gene. The nature of the sequence variants, which include mutations in the extracellular ligand-binding domain and a series of truncating mutations in the kinase domain, indicates a clear genotype-phenotype correlation between loss-of-function TGFBR1 mutations and MSSE. This distinguishes MSSE from the Marfan syndrome-related disorders in which missense mutations in TGFBR1 lead to developmental defects with vascular involvement but no reported predisposition to cancer.

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