Multiple cutaneous and uterine leiomyomata resulting from missense mutations in the fumarate hydratase gene.

Abstract:

:Multiple cutaneous and uterine leiomyomata (MCL) is an autosomal dominant disorder characterized by the development of benign smooth muscle tumours (leiomyomas) in the skin and uterus of affected women, and in the skin of affected men. In rare cases, MCL has been associated with a predisposition to the rare type II papillary renal cell cancer, also known as hereditary leiomyomatosis and renal cell cancer. The genetic locus for MCL has been mapped to chromosome 1q42.3-43 and subsequently, germline mutations in the fumarate hydratase (FH) gene have been identified. In addition, analysis of FH in some tumours of MCL patients revealed a second mutation inactivating the wild-type allele, suggesting that FH may function as a tumour suppressor gene. Here, we report two cases of MCL patients with FH mutations, designated as T287P and R190L. T287P represents a novel mutation of a highly conserved amino acid of the FH protein. In addition, a patient with an unusual clinical presentation of MCL was found to have the recurrent mutation, R190L, raising the possibility of incorporating FH sequencing as a diagnostic tool. Our findings extend the allelic series of mutations in FH and support its status as the underlying cause of MCL.

journal_name

Clin Exp Dermatol

authors

Chuang GS,Martinez-Mir A,Engler DE,Gmyrek RF,Zlotogorski A,Christiano AM

doi

10.1111/j.1365-2230.2005.01977.x

keywords:

subject

Has Abstract

pub_date

2006-01-01 00:00:00

pages

118-21

issue

1

eissn

0307-6938

issn

1365-2230

pii

CED1977

journal_volume

31

pub_type

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