title: Expansion and methylation status at FRAXE can be detected on EcoRI blots used for FRAXA diagnosis: analysis of four FRAXE families with mild mental retardation in males.
abstract: 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.
authors.affiliation: Service de Diagnostic Génétique, Institut de Chimie Biologique, Strasbourg, France.
authors.forename: V
authors.initials: V
authors.lastname: Biancalana
authors.forename: L
authors.initials: L
authors.lastname: Taine
authors.forename: J C
authors.initials: JC
authors.lastname: Bouix
authors.forename: S
authors.initials: S
authors.lastname: Finck
authors.forename: A
authors.initials: A
authors.lastname: Chauvin
authors.forename: H
authors.initials: H
authors.lastname: De Verneuil
authors.forename: S J
authors.initials: SJ
authors.lastname: Knight
authors.forename: C
authors.initials: C
authors.lastname: Stoll
authors.forename: D
authors.initials: D
authors.lastname: Lacombe
authors.forename: J L
authors.initials: JL
authors.lastname: Mandel
mesh_terms: D000293:Adolescent; D000328:Adult; D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D015246:Deoxyribonuclease EcoRI / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1; D005600:Fragile X Syndrome / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins; D010375:Pedigree; D011506:Proteins / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics*; D015534:Trans-Activators
chemical_list: D015246:Deoxyribonuclease EcoRI; D015252:Deoxyribonucleases, Type II Site-Specific; D051860:Fragile X Messenger Ribonucleoprotein 1; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D015534:Trans-Activators; C099930:AFF2 protein, human; C497683:FMR1 protein, human; C046751:endodeoxyribonuclease XmaIII