title: Validation of linkage-based DNA-diagnosis of fragile X gene carriers with the CGG repeat probe.
abstract: We have evaluated our carrier testing for the fragile X [fra(X)] syndrome, which was based on linked DNA markers, with the direct analysis of the CGG repeat sequence in the fra(X) gene. PstI and EcoRI blots were hybridized with a probe derived from the region just 3' of the CGG repeat in Xq27.3. We found the mutation analysis to be very sensitive as all 71 obligate gene carriers as well as 135 fra(X) patients tested showed evidence for an increased restriction fragment length encompassing the CGG repeat sequence with or without dispersion of the hybridization signal (mosaicism). Based on linked DNA markers, 6 out of 50 cytogenetic negative and mentally normal males at risk and 15 of 72 females at risk had inherited the allele at risk. All of these diagnoses could be confirmed by analysis of the CGG repeat length.
authors.affiliation: Department of Human Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: B A
authors.initials: BA
authors.lastname: van Oost
authors.forename: A P
authors.initials: AP
authors.lastname: Smits
authors.forename: J C
authors.initials: JC
authors.lastname: Dreesen
authors.forename: A M
authors.initials: AM
authors.lastname: van den Ouweland
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
mesh_terms: D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D015342:DNA Probes; D005069:Evaluation Studies as Topic; D005260:Female; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics*; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D008297:Male; D010375:Pedigree; D012091:Repetitive Sequences, Nucleic Acid
chemical_list: D015342:DNA Probes; D005819:Genetic Markers; D004247:DNA