Germline fumarate hydratase mutations and evidence for a founder mutation underlying multiple cutaneous and uterine leiomyomata

Multiple cutaneous and uterine leiomyomata syndrome (MCL) is an autosomal dominant disease characterized by the presence of concurrent benign tumors of smooth muscle origin (leiomyoma) in the skin and uterus of affected females, and in the skin of affected males. MCL can also be associated with type...

Full description

Saved in:
Bibliographic Details
Published in:Journal of the American Academy of Dermatology 2005-03, Vol.52 (3), p.410-416
Main Authors: Chuang, Gary S., Martinez-Mir, Amalia, Geyer, Adam, Engler, Danielle E., Glaser, Benjamin, Cserhalmi-Friedman, Peter B., Gordon, Derek, Horev, Liran, Lukash, Barbara, Herman, Eric, Cid, Manuel Prieto, Brenner, Sarah, Landau, Marina, Sprecher, Eli, Garcia Muret, Maria Pilar, Christiano, Angela M., Zlotogorski, Abraham
Format: Article
Language:English
Subjects:
Biological and medical sciences
Dermatology
Female
Founder Effect
Fumarate Hydratase - genetics
Haplotypes
Humans
Leiomyoma - genetics
Male
Medical sciences
Mutation
Pedigree
Skin Neoplasms - genetics
Uterine Neoplasms - genetics
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Multiple cutaneous and uterine leiomyomata syndrome (MCL) is an autosomal dominant disease characterized by the presence of concurrent benign tumors of smooth muscle origin (leiomyoma) in the skin and uterus of affected females, and in the skin of affected males. MCL can also be associated with type II papillary renal cell cancer (HLRCC). The genetic locus for MCL and HLRCC was recently mapped to chromosome 1q42.3-43 and subsequently, dominantly inherited mutations in the fumarate hydratase gene ( FH) were identified. Importantly, analysis of the FH gene in tumors of MCL patients revealed a second mutation inactivating the wild-type allele in some tumors. Based on these findings, it has been suggested that FH may function as a tumor suppressor gene in MCL. Here, we report the analysis of the FH gene in a group of 11 MCL families, with the identification of 8 different mutations accounting for the disease in all families. One of the mutations, 905-1G>A, has been identified in 4 families of Iranian origin. The analysis of highly polymorphic markers in the vicinity of the FH gene showed a shared haplotype in these 4 families, suggesting that 905-1G>A represents a founder mutation. Collectively, identification of 5 novel and 3 recurrent mutations further supports the role of FH in the pathogenesis of MCL.
ISSN:0190-9622
1097-6787
DOI:10.1016/j.jaad.2004.08.051