title: Novel missense mutation in the FH gene in familial renal cell cancer patients lacking cutaneous leiomyomas.
abstract: BACKGROUND
  Hereditary leiomyomatosis and renal cell cancer (HLRCC) is a rare tumor predisposition syndrome characterized by cutaneous and uterine leiomyomas and papillary type 2 renal cell cancer. Germline mutation of the fumarate hydratase (FH) gene is known to be associated with HLRCC.
  
  
  METHODS
  We describe a 64-year-old father and his 39-year-old son with HLRCC who developed papillary type 2 RCCs lacking cutaneous leiomyomas at any site. A common missense mutation in the FH gene, (c.1021G > A, p.D341N) in exon 7, was detected in the 2 cases. Functional prediction with the bioinformatics programs, SIFT and Polyphen-2, reported "damaging (SIFT score 0.00)" and "probably damaging (PSIC score 1.621)" values, respectively. In 162 healthy individuals, there were no cases of a G transition to any base. Finally, (c.1021G > A) in exon 7, was identified as a point mutation.
  
  
  CONCLUSIONS
  We report a family with HLRCC in which a novel missense mutation was detected. A familial papillary type 2 renal cancer should be considered HLRCC unless typical cutaneous leiomyomas do not occur.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Kuwada
authors.affiliation: Department of Urology, Nara Medical University, 840, Shijyo-cho, Kashihara, Japan. yychihara@gmail.com.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Chihara
authors.forename: Yi
authors.initials: Y
authors.lastname: Lou
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Torimoto
authors.forename: Yoriaki
authors.initials: Y
authors.lastname: Kagebayashi
authors.forename: Kenji
authors.initials: K
authors.lastname: Tamura
authors.forename: Taro
authors.initials: T
authors.lastname: Shuin
authors.forename: Kiyohide
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kuniyasu
authors.forename: Shoji
authors.initials: S
authors.lastname: Samma
mesh_terms: D000328:Adult; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D005091:Exons; D005649:Fumarate Hydratase / Q000235:genetics*; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D018231:Leiomyomatosis / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009386:Neoplastic Syndromes, Hereditary; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology
chemical_list: D005649:Fumarate Hydratase