Frequency of FMR1 gene mutation and CGG repeat polymorphism in intellectually disabled children in Pakistan

Abstract

Fragile X syndrome is considered the most common heritable form of X-linked intellectual disability (ID). The syndrome is caused by silencing of the fragile X mental retardation 1 gene (Xq27.3) due to hypermethylation. This mutation results in absence or deficit of its protein product, the fragile X mental retardation protein (FMRP) that affects synaptic plasticity in neurons, hence leads to brain dysfunction. The syndrome is widely distributed throughout the world. This study reported for the first time the frequency of the fragile X mental retardation 1 gene mutations in intellectually disabled children in Pakistan. We recruited 333 intellectually disabled children and 250 normal children with age ranging from 5 to 18 years for this study. Genomic DNA was extracted from peripheral blood and full mutations were identified by methylation sensitive PCR using primers corresponding to modified methylated and unmethylated DNA. Southern blot was used for confirmation of the results. The frequency of fragile X syndrome with full mutation was found as 4.8%. It was 6.5% in males as opposed to 0.9% in females; 29 CGG repeats were found as the most common allele; 31.5% in the intellectually disabled and 34% in control subjects. In Pakistan intellectual disability is considered as a social stigma for the individuals and their families. Due to lack of knowledge and cultural background people make such patients and families isolated. This study will increase public awareness about the intellectual disability and importance of prenatal screening and genetic counseling for vulnerable families.

Molecular screening for fragile X syndrome in children with unexplained intellectual disability and/or autistic behaviour

“…The frequency of fragile X-positive patients (5.7%) found in this study is consistent with the literature data reported for individuals with ID/developmental delay (2-9%). 3,[9][10][11] Similar results are observed by L. Angelova 12 among Bulgarian school-age patients with ID, but using a cytogenetic screening method. She reported a 5.9% incidence of the syndrome in a screened group of 76 boys and 25 girls.…”

Cascade Screening for Fragile X Syndrome/CGG Repeat Expansions in Children Attending Special Education in Sri Lanka

“…Small sample size of 850 is also a drawback in comparison to some similar studies reported elsewhere [ 36 ]. Two studies from Asia have reported on small samples of less than 500 [ 48 , 49 ]. However, the fact that no females with FXS were detected in our study may have been due to the small sample size.…”

Prevalence of Fragile X Syndrome among children receiving special education and carrier states in first degree relatives.

“…Also, exclusion of more prevalent conditions for intellectual impairment, such as Down syndrome in the sampling process could be seen as causing a biased over-estimation in the overall prevalence figure. However, similar exclusion criteria have been used in other studies on comparable populations [11,12]. The benefit here is that it allows for the apperception of FXS as a possible cause in those with intellectual impairment of unknown aetiology.…”

“…In contrast FXS-PM, prevalence rates are high with 1:130 to 1:256 reported for females, and 1:250 to 1:813 for males [7,8]. The rates are mostly from West European populations, but figures for other ethnically diverse populations are also known [9][10][11][12]. Prevalence rates of South Asian populations are limited.…”