Fiche publication
Date publication
octobre 1996
Journal
American journal of human genetics
Auteurs
Membres identifiés du Cancéropôle Est :
Pr MANDEL Jean-Louis
Tous les auteurs :
Biancalana V, Taine L, Bouix JC, Finck S, Chauvin A, De Verneuil H, Knight SJ, Stoll C, Lacombe D, Mandel JL
Lien Pubmed
Résumé
The original test for the analysis of the CCG expansion at the FRAXE locus involves Southern blot analysis of HindIII digests. We show that, by using a different probe, the FRAXE mutation can be detected easily on the same EcoRI or EagI+EcoRI blots as are used for detection of FRAXA. Unexpectedly, we found that both the expansion and methylation status can be determined on a single EcoRI digest, because of the presence of a methylation-sensitive EcoRI site very close to the CCG repeat. We thus detected in a series of mentally retarded individuals previously tested for FRAXA expansion a FRAXE proband who led to the identification of a large sibship (7 of 10 children carrying a mutation). We also show that two fragile X families without FRAXA mutation that previously have been described by Oberlé et al. have the FRAXE expansion. In another family also ascertained initially by cytogenetic finding of a fragile X site, we performed the combined cytogenetic and molecular prenatal diagnosis of a mutated male fetus. All nine males (>3 years old) in whom we found a methylated mutation had mild mental retardation. Our results suggest that the threshold of repeat length for abnormal methylation and fragile-site expression may be smaller at FRAXE than at FRAXA.
Mots clés
Adolescent, Adult, Blotting, Southern, Child, Child, Preschool, Chromosome Fragile Sites, Chromosome Fragility, Deoxyribonuclease EcoRI, metabolism, Deoxyribonucleases, Type II Site-Specific, metabolism, Female, Fragile X Mental Retardation Protein, Fragile X Syndrome, genetics, Humans, Infant, Infant, Newborn, Intellectual Disability, genetics, Male, Nerve Tissue Proteins, genetics, Nuclear Proteins, Pedigree, Proteins, genetics, RNA-Binding Proteins, genetics, Trans-Activators
Référence
Am. J. Hum. Genet.. 1996 Oct;59(4):847-54
