[A genetic and molecular study of 85 families affected with the fragile X syndrome]

The objective of this study was to analyze clinically, cytogenetically and molecularly 85 Spanish families with fragile X syndrome. Clinical studies were based on the score proposed by Hagerman, cytogenetic studies were made by adding. 5-fluorodeoxiuridine and molecular studies were performed by using a StB12.3 probe and the polymerase chain reaction (PCR). The results of the molecular studies in 620 individuals at risk confirmed the clinical diagnosis of fragile X syndrome in 126 affected males. In addition, 197 carrier females were detected (48 with mental retardation) and 246 "at risk" individuals and 36 non-related members were found not to have the expansion. Fifteen cases of normal transmitting males (NTM) were detected. We found one non-mentally retarded male where the CpG island of the FMR-1 gene was not methylated, but with more than 200 (CGG)n repeats (high functioning male). In the sample studied, no de novo mutations were found and all of the mutations detected were (CGG)n expansions. PCR analysis of the (CGG)n repeat in 297 normal chromosomes showed an allele distribution that ranged from 17 to 54 repeats, with an allele of 29 (CGG)n repeats accounting for 24% of the chromosomes. In conclusion, molecular genetic study of fragile X provides accurate diagnosis and facilitates genetic counselling in families with affected members. Southern blot analysis and PCR of the (CGG)n repeat provides efficient diagnosis, compared to cytogenetic techniques, for the detection of female carriers, NTMs, and prenatal diagnosis.