[A genetic and molecular study of 85 families affected with the fragile X syndrome]. / Estudio genético y molecular de 85 familias afectas del síndrome del cromosoma X frágil.

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.

[Prenatal diagnosis of cystic fibrosis, using DNA markers, in Spanish families: experience during 1987-1989]. / Diagnóstico prenatal de fibrosis quística en familias españolas utilizando marcadores del DNA: nuestra experiencia en 1987-1989.

Cystic fibrosis (CF) is the most common severe autosomal recessive disease affecting Caucasian population. Genetic linkage studies using DNA markers have allow to map the disease to chromosome 7q31-32. Several of these markers are closely enough to the CF gene, that they can be used for prenatal diagnosis of CF with a high level of confidence. We have studied 100 families with at least one affected individual. Fifteen DNA markers have been used in the present study. 96% of families were fully informatives, and 15 families requested prenatal diagnosis. A total of 17 prenatal diagnosis have been performed in these families between the 8th and the 14th week. Six fetus were diagnosed as affected and eleven as non affected of CF, with a reliability higher than 99% in all cases.