Genetic analysis in a consanguineous MCPH family revealed a refinement of the MCPH12 locus and a founder effect of the recurrent <i>CDK6</i> variant [c.589G>A, p.(Ala197Thr)] in the Pakistani population.

Primary microcephaly (MCPH) is an autosomal recessive condition of reduced head circumference due to a small cerebral cortex. Genetic studies have reported 30 MCPH genes. The aim of this study was to investigate whether the genetic mapping of the MCPH gene mutation is involved in primary microcephaly. For genetic mapping, whole exome and Sanger sequencing were performed. In this study, we identified a homozygous missense mutation, NM_001259.8:c.589G[A, p.(Ala197Thr) of <i>CDK6</i> in a consanguineous MCPH family. Since the identification of <i>CDK6</i> as a candidate gene for MCPH, this is the first report of an additional family mapping to the MCPH12locus. Molecular-genetic analysis of both families revealed an overlapping homozygous region harbouring the causal mutation in <i>CDK6</i> and a common haplotype, which led to a significant reduction of the critical MCPH12 locus. Our results suggest a founder effect of c.589G[A, p.(Ala197Thr) in the Pakistani population.