Festschrift: Professor Jenkins

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

Fahmida B Essop, Amanda Krause

Abstract


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. 


Authors' affiliations

Fahmida B Essop, Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Division of Human Genetics, National Health Laboratory Service, Johannesburg, South Africa

Amanda Krause, Division of Human Genetics, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa; Division of Human Genetics, National Health Laboratory Service, Johannesburg, South Africa

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Keywords

festschrift; Trefor Jenkins; human genetics; fragile X syndrome; genetic testing

Cite this article

South African Medical Journal 2013;103(12):994-998. DOI:10.7196/SAMJ.7144

Article History

Date submitted: 2013-06-07
Date published: 2013-10-11

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