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

Gary S. Chuang*, Amalia Martinez-Mir, Adam Geyer, Danielle E. Engler, Benjamin Glaser, Peter B. Cserhalmi-Friedman, Derek Gordon, Liran Horev, Barbara Lukash, Eric Herman, Manuel Prieto Cid, Sarah Brenner, Marina Landau, Eli Sprecher, Maria Pilar Garcia Muret, Angela M. Christiano, Abraham Zlotogorski

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)410-416
Number of pages7
JournalJournal of the American Academy of Dermatology
Issue number3 Pt 1
StatePublished - Mar 2005
Externally publishedYes


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