title: Mutation screening of fumarate hydratase by multiplex ligation-dependent probe amplification: detection of exonic deletion in a patient with leiomyomatosis and renal cell cancer.
abstract: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a syndrome predisposing to cutaneous and uterine leiomyomatosis as well as renal cell cancer and uterine leiomyosarcoma. Heterozygous germline mutations in the fumarate hydratase (FH, fumarase) gene are known to cause HLRCC. On occasion, no FH mutation is detected by direct sequencing, despite the evident HLRCC phenotype in a family. In the present study, to investigate whole gene or exonic deletions and amplifications in FH mutation-negative patients, we used multiplex ligation-dependent probe amplification technology. The study material comprised 7 FH mutation-negative HLRCC patients and 12 patients affected with HLRCC-associated phenotypes, including papillary RCC, early-onset RCC, uterine leiomyomas, or uterine leiomyosarcoma. A novel FH mutation, a deletion of FH exon 1 that encodes the mitochondrial signal peptide, was detected in one of the HLRCC patients (1/7). The patient with the FH mutation displayed numerous painful cutaneous leiomyomas and papillary type renal cell cancer. Our finding, together with the two patients with whole FH gene deletion who had been detected previously, suggests that exonic or whole-gene FH deletions are not a frequent cause of HLRCC syndrome.
authors.affiliation: Department of Medical Genetics, Biomedicum Helsinki, University of Helsinki, PO Box 63, FI-00014 Helsinki, Finland.
authors.forename: Taru
authors.initials: T
authors.lastname: Ahvenainen
authors.forename: Heli J
authors.initials: HJ
authors.lastname: Lehtonen
authors.forename: Rainer
authors.initials: R
authors.lastname: Lehtonen
authors.forename: Pia
authors.initials: P
authors.lastname: Vahteristo
authors.forename: Kristiina
authors.initials: K
authors.lastname: Aittomäki
authors.forename: Gareth
authors.initials: G
authors.lastname: Baynam
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dommering
authors.forename: Charis
authors.initials: C
authors.lastname: Eng
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Gruber
authors.forename: Henrik
authors.initials: H
authors.lastname: Grönberg
authors.forename: Rauno
authors.initials: R
authors.lastname: Harvima
authors.forename: Riitta
authors.initials: R
authors.lastname: Herva
authors.forename: Marja
authors.initials: M
authors.lastname: Hietala
authors.forename: Minna
authors.initials: M
authors.lastname: Kujala
authors.forename: Helena
authors.initials: H
authors.lastname: Kääriäinen
authors.forename: Lone
authors.initials: L
authors.lastname: Sunde
authors.forename: Outi
authors.initials: O
authors.lastname: Vierimaa
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Pollard
authors.forename: Ian P M
authors.initials: IP
authors.lastname: Tomlinson
authors.forename: Erik
authors.initials: E
authors.lastname: Björck
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Virpi
authors.initials: V
authors.lastname: Launonen
mesh_terms: D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D017931:DNA Primers; D005091:Exons; D005649:Fumarate Hydratase / Q000235:genetics*; D006801:Humans; D018231:Leiomyomatosis / Q000235:genetics*; D022521:Ligase Chain Reaction; D009154:Mutation; D017384:Sequence Deletion
chemical_list: D017931:DNA Primers; D005649:Fumarate Hydratase