Molecular study of a consanguineous family with autosomal recessive mental retardation and speech disorder

Mental retardation (MR) is one of the most frequently found major genetic disorders around the world, affecting 1-3% of the people in the general population. The recent advancement in molecular biology and cytogenetic study has made possible the identification of new genes for a variety of genetic disorders including autosomal recessive MR. Recessive genetic disorders are common in Pakistan due to the high rate of consanguinity. A central focus of the present study was to map and identify the disease causing gene in a mentally retarded consanguineous Pakistani family with speech disorder. The study comprises of 20 individuals including 10 patients. Genetic analysis of autosomal recessive MR and speech disorders was carried out for eight known fundamental loci sorted out on the basis of clinical features. These loci including 3p26.2, 3p21.3, 7q22, 8p22, 11p15, 14q11.2-q12, 19p13.12, and 22p13 were screened using polymorphic microsatellite markers. To identify the disease locus, genomic DNA from each individual was genotyped for homozygosity analysis. Microsatellite markers were amplified using PCR. The study provided valuable data to exclude linkage of the above mentioned loci. The absence of any linkage of the Pakistani family with autosomal recessive MR to the eight well known loci, confirms the genetic heterogeneity of MR. These results need to be verified and the candidate gene be found by a complete genome scan, which may help us in establishing the genotype-phenotype correlation of MR, improving genetic counseling, carrier screening, DNAbased prenatal diagnosis and the opportunity to develop appropriate animal models to test new forms of cell or gene therapies.