Cytogenetic versus DNA diagnosis in routine referrals for fragile X syndrome

The molecular cloning of the gene that causes the fragile X syndrome, and the demonstration that the causative mutation is an expansion of an unstable trinucleotide repeat, suggests that cytogenetic testing could be replaced by a molecular test. We compared the two methods in 525 routine referrals. 12 cases were positive in both tests. 1 case that had a negative DNA test for the fragile site at Xq27.3 (FRAXA), but a positive cytogenetic result, was shown to be caused by a mutation at the FRAXE locus on chromosome Xq28. DNA analysis is a sensitive, reliable, and cost-effective diagnostic alternative.