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

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.