Novel and recurrent ASPM mutations of founder effect in Chinese population.

Purpose: Mutations in ASPM are the most common causes of primary microcephaly (MCPH), which is a rare brain developmental disorder with few studies in Chinese population so far. This study aimed to identify the common pathogenic variants of ASPM and estimated the incidence of MCPH5 in Guangxi population.

Methods: We ascertained six MCPH cases caused by ASPM mutations in Guangxi Zhuang Autonomous Region, Whole-exome sequencing (WES) was performed to uncover the causal variants. The haplotype analysis was used to estimate the age of the recurrent variation.

Results: Five different pathogenic variants were identified in this batch of MCPH5 cases, including two novel variants p.Ser842fs*9 and p.Lys1340Argfs*29. An rarely reported pathogenic variant, c.1789C>T/p.Arg597* was found to be a founder mutation in local population. We evaluated all ASPM variants detected among 2674 non-microcephalic individuals and estimated the MCPH5 incidence to be 5.03/1,000,000 in Guangxi population.

Conclusions: We reported the first case series of Chinese MCPH cases with ASPM mutation and revealed a highly recurrent founder mutation in this local population. MCPH5 may be the major type of congenital microcephaly in Chinese population.