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

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 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 FMR-1 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 the 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.

FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile

“…The overall frequency detected is relatively higher compared to other ID populations, which show overall ranges in males between 1 and 5·2% (Crawford et al, 2001;Essop & Krause, 2013). Of them, 6·7% were males and 1·5% females.…”

“…Although, a number of studies have been carried out reporting prevalence of FXS in different populations (Crawford et al, 2001;Puusepp et al, 2008;Essop & Krause, 2013;Tejada et al, 2014), knowledge in Latin America is relatively scant (Lacassie et al, 1983;Florencia et al, 2006;Christofolini et al, 2009). Although, a number of studies have been carried out reporting prevalence of FXS in different populations (Crawford et al, 2001;Puusepp et al, 2008;Essop & Krause, 2013;Tejada et al, 2014), knowledge in Latin America is relatively scant (Lacassie et al, 1983;Florencia et al, 2006;Christofolini et al, 2009).…”

Fragile X checklists: A meta‐analysis and development of a simplified universal clinical checklist

“…It shows that six studies were from North America and Europe (Arvio, Peippo, & Simola, 1997;Bellavance & Morin, 2017;Butler, Brunschwig, Miller, & Hagerman, 1992;Hagerman et al, 1991;Lachiewicz, Dawson, & Spiridigliozzi, 2000;de Vries, Halley, Oostra, & Niermeijer, 1998), two from South to Central Asia (Guruju et al, 2009;Kanwal et al, 2015), two from Latin America and the Caribbean (Boy, Correia, Llerena, Machado-Ferreira, & Pimentel, 2001;Christofolini et al, 2009), and one from Africa (Behery, 2008). We did come across two interesting fragile X syndrome studies from Sub-Saharan Africa, but none of them met the criteria to be included in this study (Essop & Krause, 2013;Peprah, Allen, Williams, Woodard, & Sherman, 2010). One American cohort was multiethnic, including African-American patients.…”

Understanding the genetic diversity of South Africa’s peoples

“…Fragile X mental retardation syndrome is the commonest cause of intellectual disability in all the local SA populations, [3] as it is worldwide. It was previously thought to be rare in blacks, but this was due to under-ascertainment.…”