Mutation analysis of ASPM gene in two Pakistani Famillies with autosomal recessive primary microcephaly

Autosomal recessive primary microcephaly (MCPH) is a disorder of fetal brain growth, with reduced head circumference. The affected individuals exhibit reduced occipital-frontal head circumference (>2 SD) and mild-to-severe mental retardation. Autosomal recessive primary microcephaly is genetically heterogeneous and 18 loci have been reported to date. Mutations in ASPM gene are the most common cause of MCPH in the majority of the cases. The objective of the study was to search for pathogenic mutations in two Pakistani families with autosomal recessive primary microcephaly. In the current investigation, we have identified a previously reported mutation in ASPM gene. DNA samples of all available affected and unaffected individuals were PCR amplified using microsatellite markers and further analyzed by DNA sequencing. DNA sequence analysis revealed a previously reported mutation (p.W1326*) in ASPM gene. This study furthur validate that mutations in ASPM are the major cause of autosomal recessive primary microcephaly in the Pakistani population.