[DNA diagnosis of fragile X syndrome in a family. A new type of heredity--dynamic mutations].

In typical cases, the diagnosis of fragile X syndrome can be made clinically, but has so far been based on cytogenetic detection of a fragile site on the X chromosome at Xq27.3. Cytogenetic analyses are time-consuming, and false negative results have been a problem. Following the successful molecular cloning of the gene causing the fragile X syndrome, a novel genetic principle was discovered: the "dynamic" DNA mutation. DNA analyses have now the power to distinguish between normal copies of the gene, carrier mutations and fragile X mutations. We have performed both cytogenetic and DNA analyses in an extended fragile X family. DNA fragment length variations in the gene were identified by Southern blot analysis, and the results were used diagnostically in the family. Instability of the mutation (dynamic mutation) occurred between generations and within individuals. DNA analysis, as performed here, improves diagnostic accuracy and genetic counselling in fragile X families.