Consanguinity and Autosomal Recessive Mental Retardation in South Waziristan Agency

Mental Retardation (MR) is characterized by significant limitations in intellectual functioning and adaptive skills occurred before the ages of 18 years. Previously extensive work was done on X-linked MR but now the research work is going on identifying new genes and locus related to autosomal recessive MR. We focused on consanguineous families from South Waziristan Agency (SWA) for linkage analysis of autosomal recessive MR locus. The consanguineous families possessing at least two effected individuals were selected for the study. DNA was extracted by non-organic method and quantitatively measured by NanoDrop spectrophotometer. The DNA of selected families was amplified through touchdown PCR for any possible linkage to already reported MR loci. Linkage analysis was carried out, using microsatellite markers for each locus with forward primer labeled with one of the fluorescent dyes, FAM, VIC, HEX or NED. Linkage was found in family PKMR438 to the locus MRT6, showing that the candidate gene GRIK2 in this region was responsible for MR. Though families PKMR436 and PKMR442 were not linked to known loci but PKMR435 gave a clue of linkage to MRT4 with a marker but, by using genome-wide markers near MRT4 could confirm the linkage. The clinical findings revealed reduced head circumference and deformed hands and feet and difficulties even in sitting in certain patients while no such abnormalities were there in some affected individuals thus showing heterogeneity of autosomal recessive MR genes. We thus assume that more than 50% consanguineous families in this region may show linkage to autosomal recessive MR loci. The X-linked cases may show greater percentage that needs to be explored.