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Novel and recurrent ASPM mutations of founder effect in Chinese population

  • Mengting Li
    Affiliations
    Department 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
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  • Jingrong Luo
    Affiliations
    Department 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
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  • Qi Yang
    Affiliations
    Department 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
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  • Fei Chen
    Affiliations
    Department 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
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  • Jie Chen
    Affiliations
    Department of Obstetrics, The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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  • Jiayi Qin
    Affiliations
    Department of Obstetrics, The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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  • Wei He
    Affiliations
    Department of Obstetrics, The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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  • Junjie Chen
    Affiliations
    Radiology Department, The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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  • Sheng Yi
    Affiliations
    Department 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
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  • Zailong Qin
    Affiliations
    Department 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
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  • Shang Yi
    Affiliations
    Department 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
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  • Limei Huang
    Affiliations
    Department 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
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  • Xiaoxia Qiu
    Affiliations
    Department 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
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  • Pingshan Pan
    Affiliations
    Department of Obstetrics, The Maternal and Child Health Care Hospital of Guangxi Zhuang Autonomous Region, Nanning, China
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  • Jingsi Luo
    Correspondence
    Corresponding authors at: Department 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.
    Affiliations
    Department 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
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  • Yiping Shen
    Correspondence
    Corresponding authors at: Department 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.
    Affiliations
    Department 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

    Department of Medical Genetics and Molecular Diagnostic Laboratory, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China

    Division of Genetics and Genomics, Boston Children's Hospital, Department of Neurology, Harvard Medical School, Boston, USA
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      Abstract

      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.

      Keywords

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