Diagnostic molecular genetics of the fragile X

The approaches to carrier detection and prenatal diagnosis of the fragile X syndrome using DNA probes are described. Since the definitive diagnosis rests upon the cytogenetic demonstration of the fragile X, molecular diagnoses are essentially confined to fragile X family members in whom the fragile X cannot be demonstrated. Since none of the polymorphic probes available are tightly linked to the fragile X, the preferred approach is to use probes which flank the fragile site. Useful probes are listed and suggested recombination fractions for use in diagnosis are given. A strategy is outlined for obtaining the closest informative flanking markers with the minimum amount of laboratory effort. Methods of risk analysis are discussed. It is concluded that molecular analysis is very useful for carrier detection but of limited use in prenatal diagnosis.