title: Complete Penetrance and Absence of Intrafamilial Variability in a Large Family with Hereditary Leiomyomatosis and Renal Cell Carcinoma.
abstract: BACKGROUND
  Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant familial disorder due to FH mutation. Despite a considerable increase in information about the genetic background, inter- and intrafamilial phenotypic variability/penetrance are not well documented.
  
  
  OBJECTIVE
  To describe a large French HLRCC family and provide new data on penetrance and intrafamilial variability.
  
  
  METHODS
  The whole family was contacted for clinical examination, skin biopsy, uterine and kidney imagery and molecular analysis.
  
  
  RESULTS
  The family included 22 members in 3 generations. The second generation consisted of 13 members who were older than the expected age of onset of disease manifestations. Of the 12 available members of this second generation, 6 (1 man and 5 women, aged 44-57 years) had a novel FH mutation. All had the same mild phenotype with cutaneous asymptomatic leiomyomas, uterine fibroids (if women) and no kidney tumor. The other 6 members not bearing the familial mutation had normal clinical and radiological findings. In this second generation, the penetrance was therefore complete, and there was no intrafamilial variability in the clinical expression of the mutation.
  
  
  CONCLUSIONS
  This study provides additional data on genotype/phenotype correlation, intrafamilial variability and penetrance that should help to improve prognosis and genetic counseling.
authors.affiliation: Service de Dermatologie, CHU Larrey, Universitx00E9; Paul Sabatier, Toulouse, France.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Guinard
authors.forename: Laureline
authors.initials: L
authors.lastname: Legendre
authors.forename: Nora
authors.initials: N
authors.lastname: Kramkimel
authors.forename: Marie Françoise
authors.initials: MF
authors.lastname: Avril
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chassaing
authors.forename: Odile
authors.initials: O
authors.lastname: Cabaret
authors.forename: Marine
authors.initials: M
authors.lastname: Guillaud-Bataille
authors.forename: Juliette
authors.initials: J
authors.lastname: Mazereeuw Hautier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001706:Biopsy; D002292:Carcinoma, Renal Cell / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005190:Family; D005260:Female; D005649:Fumarate Hydratase / Q000235:genetics* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D018231:Leiomyomatosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D011379:Prognosis; D012867:Skin / Q000473:pathology; D055815:Young Adult
chemical_list: D004247:DNA; D005649:Fumarate Hydratase