The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening.
Fiche publication
Date publication
novembre 2009
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BINQUET Christine, Pr CLAVEL Christine
Tous les auteurs :
Thauvin-Robinet C, Munck A, Huet F, Genin E, Bellis G, Gautier E, Audrezet MP, Ferec C, Lalau G, Georges MD, Claustres M, Bienvenu T, Gerard B, Boisseau P, Cabet-Bey F, Feldmann D, Clavel C, Bieth E, Iron A, Simon-Bouy B, Costa C, Medina R, Leclerc J, Hubert D, Nove-Josserand R, Sermet-Gaudelus I, Rault G, Flori J, Leroy S, Wizla N, Bellon G, Haloun A, Perez-Martin S, d'Acremont G, Corvol H, Clement A, Houssin E, Binquet C, Bonithon-Kopp C, Alberti-Boulme C, Morris MA, Faivre L, Goossens M, Roussey M
Lien Pubmed
Résumé
BACKGROUND: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. METHODS: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (p(R117H)), on either intron 8 T5 or T7 background, and F508del (p(F508del)) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. RESULTS: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p(F508del) was 1.06%, p(R117H;T7) 0.27% and p(R117H;T5)
Référence
J Med Genet. 2009 Nov;46(11):752-8