Diagnostic, carrier and prenatal genetic testing for fragile X syndrome and other FMR-1-related disorders in Johannesburg, South Africa: a 20-year review.

BACKGROUND Fragile X syndrome (FXS), the most common inherited cause of intellectual disability (ID) worldwide, is caused by the expansion of a CGG repeat in the fragile X mental retardation gene (FMR-1) gene. OBJECTIVES; To review, retrospectively, the genetic services for FXS and other FMR-1-related disorders - including fragile X-associated tremor/ataxia syndrome (FXTAS) and FMR-1-related primary ovarian insufficiency (POI) - at the Division of Human Genetics, Johannesburg, for diagnostic, carrier and prenatal genetic testing.Methods. The records of 2 690 patients with ID and suspected FXS (ID/?FXS) who had genetic testing for FMR-1 between 1992 and 2012 were reviewed. Of these, 2 239 had diagnostic testing, 430 carrier or cascade testing and 17 prenatal testing for FXS. Four had FXTAS or POI testing. Polymerase chain reaction (PCR) and/or Southern blotting techniques were used to test the patients' samples for FMR-1 and FMR-2 expansions. RESULTS; Of the 2 239 patients who had diagnostic testing, 128 (5.7%) had a full mutation, 12 (0.5%) had a premutation and 43 (1.9%) an intermediate allele. In 17 prenatal tests, eight fetuses tested positive for FXS. FMR-1 CGG repeat distribution analysis in 1 532 males negative for the FMR-1 expansion showed that 29 and 30 CGG repeats were the most common (61.1%), but distribution was significantly different in the black and white populations.CONCLUSION; The findings support the presence of FXS, as the most common cause of ID, in all local populations. The FMR-1 CGG repeat distribution varied from that found in other studies. The number of family members tested was relatively low suggesting that many at-risk individuals are not being referred.