Prenatal diagnosis of fragile X syndrome by direct detection of the unstable DNA sequence

FRAGILE X syndrome is the most common form of familial mental retardation.¹ Its prenatal diagnosis has relied on cytogenetic detection of the fragile X chromosome in cultured amniotic fluid, chorionic-villus cells, or fetal blood obtained by cordocentesis. The rate of misdiagnosis is about 5 percent and is due to rare false positive and more frequent false negative diagnoses.² A molecular-genetic approach using DNA polymorphisms linked to the fragile site is feasible for diagnosis, but the results are probabilistic rather than absolutely diagnostic.^3,4 The fragile X syndrome has recently been shown to be characterized by an unstable DNA sequence that can.