Fragile X mental retardation syndrome: DNA diagnosis and carrier detection in New Zealand families.
OBJECTIVE
To establish a DNA-based test for the diagnosis and carrier detection of fragile X syndrome, and to investigate the nature of the mutation and patterns of inheritance in New Zealand families.


METHODS
A probe for the FRAXA region was generated by polymerase chain reaction, cloned in a plasmid vector, and its structure was confirmed by DNA sequencing. This probe was used in a Southern blot assay to detect full mutations or premutations associated with fragile X syndrome in DNA from peripheral blood samples submitted to our laboratory for routine testing.


RESULTS
We tested 379 individuals from throughout New Zealand. Full mutations were found in 29 males, leading to a fragile X diagnosis, or confirmation of an earlier cytogenetic diagnosis. Premutations were detected in 45 females and 11 males, all of whom are asymptomatic carriers of the disease.


CONCLUSIONS
The DNA test is rapid and accurate, in contrast to the cytogenetic test. It allows unequivocal detection of carriers, enabling effective counselling, prenatal testing, and more generalised screening of at-risk populations. Our discovery of one 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.
D015139:Blotting, Southern; D003001:Cloning, Molecular; D004247:DNA / Q000032:analysis*; D015342:DNA Probes; D005260:Female; D005600:Fragile X Syndrome / Q000175:diagnosis / Q000235:genetics*; D006580:Genetic Carrier Screening; D005817:Genetic Counseling; D005822:Genetic Vectors; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D009520:New Zealand; D010375:Pedigree; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011296:Prenatal Diagnosis; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA
D015342:DNA Probes; D004247:DNA