Autozygosity mapping in consanguineous Pakistani families identifies nine non-overlapping novel linkage intervals for autosomal recessive non-syndromic mental retardation (AR-NSMR); shows genetic heterogeneity for AR-NSMR.

Psychological disturbance (PD) or cerebral dysfunction (CD) covers several clinical areas, and has defining features of mental retardation. Recently, we conducted a study to investigate heritable heterogeneity in Pakistani consanguineous couples with recessive autosomal intellectual abnormalities. A cohort of three consanguineous families with multiple birth defects, belonging two to district lower Dir and one to district Lodhra, were selected for molecular analysis. All the affected individuals in the cohort showed autosomal recessive non-syndromic mental disturbances. DNA was extracted and subjected to Single tagged sequence (STS) marker analyses to all known non-syndromic autosomal recessive mental retardation (NS-ARMR) genes, while autozygosity mapping was performed by advanced SNP techniques. Fragment analyses of the NS-ARMR disease genes CRBN, CC2D2A, PRSS12, GRIK2, TUSC3, and CC2D1A using polymorphic STS markers confirmed these to be contender genes for the alteration. Mapping of autozygosity in all the study subjects using genome study revealed nine novel linkage intervals, i.e. four intervals for MR4, two intervals for MR8 and three intervals for MR13. In spite of being a monogenic condition, autosomal recessive mental retardation shows genetic heterogeneity and several genes are involved in different families; hence, there is a chance for involvement of separate gene in each family.