FRAGILE-X MENTAL-RETARDATION SYNDROME - DNA DIAGNOSIS AND CARRIER DETECTION IN NEW-ZEALAND FAMILIES

Aims. To establish a DNA-based test for the diagnosis and carrier dete ction of fragile X syndrome, and to investigate the nature of the muta tion and patterns of inheritance in New Zealand families. Methods. A p robe for the FRAXA region was generated by polymerase chain reaction, cloned in a plasmid vector, and its structure was confirmed by DNA seq uencing. This probe was used in a Southern blot assay to detect full m utations or premutations associated with fragile X syndrome in DNA fro m peripheral blood samples submitted to our laboratory for routine tes ting. Results. We tested 379 individuals from throughout New Zealand. Full mutations were found in 29 males, leading to a fragile X diagnosi s, or confirmation of an earlier cytogenetic diagnosis. Premutations w ere detected in 45 females and 11 males, all of whom are asymptomatic carriers of the disease. Conclusions. The DNA test is rapid and accura te, in contrast to the cytogenetic test. It allows unequivocal detecti on of carriers, enabling effective counselling, prenatal testing, and more generalised screening of at-risk. populations. Our discovery of o ne large pedigree with many carriers and no prior history of X-linked mental retardation demonstrates that the DNA test is appropriate even in apparently sporadic cases of mental retardation.