FRAXA locus in fragile X diagnosis: family studies, prenatal diagnosis, and diagnosis of sporadic cases of mental retardation.
Three hundred eighty-seven individuals from 32 Finnish fragile X families were studied, using the probe StB12.3 [Oberlé et al., 1991: Science 252:1097-1102] for the FRAXA locus, to reveal length variations in the FMR-1 gene. As expected, the affected individuals (with few exceptions) showed a full mutation; a few affected individuals with a premutation only were found. Seventy percent of the females with a full mutation were affected. The size of the mutation remained unchanged in 6, increased in 73, and decreased in 6 female meioses. In male meioses the size was unchanged in 15 cases, increased in 2 cases, and decreased in 1 case. Prenatal diagnosis was performed in 20 cases. In 7 of these the mutation was inherited by the fetus. Four hundred sixty-four mentally retarded patients were referred to us for FRAXA analysis. In 5% of these the fragile X mutation was found. In addition to the clear cut negative or positive results there were 6 cases in which an increase of 50-80 bp was detected. These findings may represent either large normal alleles or small premutations suggesting a possible tissue mosaicism which could explain the retardation of the patients.
von Koskull
H
H
Department of Obstetrics and Gynecology, Helsinki University Hospital, Finland.
Gahmberg
N
N
Salonen
R
R
Salo
A
A
Peippo
M
M
D000649:Amniocentesis; D015193:Chorionic Villi Sampling; D002873:Chromosome Fragility; D004252:DNA Mutational Analysis; D015342:DNA Probes; D003937:Diagnosis, Differential; D015226:Dinucleoside Phosphates / Q000378:metabolism; D005260:Female; D005600:Fragile X Syndrome / Q000175:diagnosis*; D006580:Genetic Carrier Screening / Q000379:methods*; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis; D008297:Male; D008745:Methylation; D009030:Mosaicism; D011237:Predictive Value of Tests; D011296:Prenatal Diagnosis / Q000379:methods*; D014960:X Chromosome / Q000235:genetics
D015342:DNA Probes; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide