Germline fumarate hydratase mutations in families with multiple cutaneous and uterine leiomyomata

Germline mutations in the famarate hydratase gene (FH) predispose to multiple cutaneous and uterine leiomyoma syndrome (MCL) and MCL associated with renal cell cancer. MCL is inherited in an autosomal dominant pattern, manifesting as skin leiomyoma and uterine fibroids in affected individuals. Fumarate hydratase, a component of the tricarboxylic acid cycle, acts as a tumor suppressor gene in the development of cutaneous and uterine leiomyoma and renal cell cancer in this syndrome. Here we report the clinical and mutational analysis of five families with MCL, with the identification of five new mutations affecting highly conserved residues of the FH protein. These results provide further evidence for the role of the FH gene in the pathogenesis of MCL.