title: Strong family history of uterine leiomyomatosis warrants fumarate hydratase mutation screening.
abstract: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and renal cell cancer. HLRCC is caused by heterozygous germline mutations in the fumarate hydratase (FH) gene. A Finnish family with nine closely related women with uterine leiomyomas was detected by an alert gynecologist. No cutaneous or renal cell tumors were reported in the family when it was referred to genetic analyses. Samples were available from seven patients, and a novel germline FH mutation was detected in five of them. Mutation carriers were symptomatic, had multiple tumors and were diagnosed at an early age. This study emphasizes the importance of considering FH mutation screening when gynecologists encounter families with multiple severe uterine leiomyoma cases. Due to possibility of phenocopies more than one patient should be tested. Early mutation detection allows regular screening of the mutation carriers and enables early detection of possible highly aggressive renal tumors. It may also affect family planning as multiple myomas at early age may significantly reduce fertility.
authors.affiliation: Department of Medical Genetics, Genome-Scale Biology Research Program, University of Helsinki, Helsinki, Finland.
authors.forename: Jaana
authors.initials: J
authors.lastname: Tolvanen
authors.forename: Outi
authors.initials: O
authors.lastname: Uimari
authors.forename: Markku
authors.initials: M
authors.lastname: Ryynänen
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Pia
authors.initials: P
authors.lastname: Vahteristo
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D005260:Female; D005387:Finland; D005649:Fumarate Hydratase / Q000235:genetics*; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics; D007889:Leiomyoma / Q000235:genetics*; D018231:Leiomyomatosis / Q000235:genetics; D008875:Middle Aged; D009386:Neoplastic Syndromes, Hereditary / Q000235:genetics; D010375:Pedigree; D012878:Skin Neoplasms; D014594:Uterine Neoplasms / Q000235:genetics*
chemical_list: D005649:Fumarate Hydratase