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Novel and recurrent ASPM mutations of founder effect in Chinese population

Mengting Li1, Jingrong Luo1, Qi Yang1

  • 1Department of Genetic and Metabolic Central Laboratory, The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Guangxi Birth Defects Prevention and Control Institute, Nanning, China.

Brain & Development
|May 1, 2022
PubMed
Abstract

Insights

Mutations in ASPM cause primary microcephaly (MCPH), a rare brain disorder. This study identified common ASPM variants and a founder mutation in China, estimating MCPH5 incidence in the Guangxi population.

Area of Science:

  • Genetics
  • Developmental Biology
  • Neurology

Background:

  • Primary microcephaly (MCPH) is a rare neurodevelopmental disorder characterized by reduced brain size.
  • Mutations in the ASPM gene are a leading genetic cause of MCPH.
  • Limited research exists on ASPM mutations within the Chinese population.

Purpose of the Study:

  • To identify common pathogenic variants in the ASPM gene in Chinese MCPH patients.
  • To estimate the incidence of MCPH subtype 5 (MCPH5) in the Guangxi population.
  • To investigate the prevalence and origin of ASPM mutations in this region.

Main Methods:

  • Ascertainment of six MCPH cases with suspected ASPM mutations in Guangxi.
  • Whole-exome sequencing (WES) to identify causative genetic variants.
  • Haplotype analysis to determine the age of recurrent mutations.

Main Results:

  • Identification of five distinct pathogenic ASPM variants, including two novel mutations (p.Ser842fs*9 and p.Lys1340Argfs*29).
  • Discovery of a founder mutation (c.1789C>T/p.Arg597*) prevalent in the local population.
  • Estimation of MCPH5 incidence at 5.03 per 1,000,000 in the Guangxi population, based on variant frequencies in 2674 controls.

Conclusions:

  • This study presents the first case series of Chinese MCPH patients with ASPM mutations.
  • A highly recurrent founder mutation in ASPM was identified in the Guangxi population.
  • MCPH5 is suggested to be a predominant form of congenital microcephaly among the Chinese population.
Keywords:
ASPMFounder effectMCPH5Primary microcephaly

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