A Molecular Genetic Study of Autosomal Recessive Primary Microcephaly in three Pakistani Kindred

Microcephaly (MCPH) is a condition with architecturally normal brain but reduced head of occipito-frontal circumference below -2 or -3 standard deviation. Primary microcephaly is present at birth leading to non-progressive mental retardation, affecting 2-2.5% of the total population and is more prevalent in Asia and Arab than Europe. About 50% individuals with primary microcephaly have an ASPM mutation that is the most common cause of MCPH in Pakistan. In this present study exclusion mapping of three different families of primary microcephaly was done. DNA was isolated from three affected families (MCP1, MCP2 and MCP3) and PCR was followed by non-denaturing polyacrylamide gel electrophoresis. One family MCP1 showed complete linkage with locus 5 (MCPH5) on chromosome 1q31. Second family MCP2 linked at locus 2 on chromosome 19q13.1-13.2 and third family MCP3 did not linked with any of the known locus (MCPH1-MCPH7). The heterozygous pattern of affected individuals was found for MCP3 family during screening of all known loci. This finding suggested the plausibility of a novel locus, so genome wide search of MCP1 family should be supportive in future, which would lead to the mapping of a novel region associated with primary microcephaly.