Fragile X Syndrome (FXS), an X-linked dominant monogenic condition, is the main genetic cause of intellectual disability (ID) and autism spectrum disorder (ASD). FXS is associated with an expansion of CGG repeat sequence in the Fragile X Mental Retardation gene 1 (FMR1) on chromosome X. Following a neuropediatric assessment of two male siblings who presented with signs of FXS that was confirmed with molecular testing, we provided cascade counselling and testing to the extended family. A total of 46 individuals were tested for FXS; among them, 58.70% (n = 27) were females. The mean age was 9.4 (±5) years for children and 45.9 (±15.9) years for adults. Pedigree analysis suggested that the founder of these families was likely a normal transmitting male. Four out of 19 males with clinical ID were confirmed to have a full mutation for FXS, while 14/27 females had a pathologic CGG expansion (>56 CGG repeats) on one of their X chromosomes. Two women with premature menopause were confirmed of being carriers of premutation (91 and 101 CGG repeats). We also identified maternal alleles (91 and 126 CGG repeats) which expanded to a full mutation in their offspring (>200 CGG repeats). This study is a rare report on FXS from Africa and illustrates the case scenario of implementing genetic medicine for a neurogenetic condition in a rural setting.
Keywords: Africa; Cameroon; fragile X syndrome; full mutation; genetic counselling; premutation.
Conflict of interest statement
The authors declare no competing interest.
Fragile X spectrum disorders.Intractable Rare Dis Res. 2014 Nov;3(4):134-46. doi: 10.5582/irdr.2014.01022. Intractable Rare Dis Res. 2014. PMID: 25606363 Free PMC article. Review.
Fragile X Syndrome.2020 Apr 13. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. StatPearls. 2020 Jan–. PMID: 29083768 Free Books & Documents. Review.
An assessment of screening strategies for fragile X syndrome in the UK.Health Technol Assess. 2001;5(7):1-95. doi: 10.3310/hta5070. Health Technol Assess. 2001. PMID: 11262423 Review.
Autism spectrum disorders and attention-deficit/hyperactivity disorder in boys with the fragile X premutation.J Dev Behav Pediatr. 2006 Apr;27(2 Suppl):S137-44. doi: 10.1097/00004703-200604002-00012. J Dev Behav Pediatr. 2006. PMID: 16685180
FMR1 gene mutations in patients with fragile X syndrome and obligate carriers: 30 years of experience in Chile.Genet Res (Camb). 2016 Jun 28;98:e11. doi: 10.1017/S0016672316000082. Genet Res (Camb). 2016. PMID: 27350105 Free PMC article.