The Diagnosis of Fragile X Syndrome

Résumé du livre

Fragile X syndrome, an X-linked condition of mental handicap with typical clinical features, has traditionally been diagnosed by the observation of a folate dependent fragile site at the distal end of Xq. Since the recent identification of an expansion mutation in a gene, FMR-1, in fragile X families, the possibility of using a DNA assay as an alternative diagnostic method has become available. A retrospective review of referrals for cytogenetic diagnosis of fragile X syndrome showed a shortfall of diagnosed pedigrees compared to prevalence estimates. Approximately 25% developmentally delayed children in South East Thames were tested for fragile X, and 28% of the predicted number of affected males were diagnosed. A pilot study screening 3 special school populations resulted in the diagnosis of one affected boy from a total of 97 children tested. DNA and cytogenetic assays for fragile X were compared for a series of 157 referrals, no conflicting results were obtained. Clinical examination of 39 affected males and 11 affected females confirmed the variability of the syndrome. Ovarian volume was measured in a cohort of intellectually normal heterozygotes and was shown to be normal. The presence of the expansion mutation in 42 pedigrees previously diagnosed as ·affected with fragile X syndrome was studied. Linear relationships were demonstrated between expansion size and chromosome fragility in heterozygous females, and between a clinical score and expansion size in affected males and females. The detection of the mutation in family members was more informative than cytogenetic and clinical assessments. In 4 out of 42 previously diagnosed fragile X pedigrees no expansion mutation was detected. 3 of these pedigrees were shown to have the fragile site FRAXE, and the fourth a novel fragile site, FRAXF. Three cases of aneuploidy coincident with fragile X are discussed.