Case report: A novel CASK mutation in a Chinese female child with microcephaly with pontine and cerebellar hypoplasia

Guilan Xie; Yan Zhang; Wenfang Yang; Liren Yang; Ruiqi Wang; Mengmeng Xu; Landi Sun; Boxing Zhang; Xiaoyi Cui

doi:10.3389/fgene.2022.856636

Case report: A novel CASK mutation in a Chinese female child with microcephaly with pontine and cerebellar hypoplasia

Front Genet. 2022 Sep 7:13:856636. doi: 10.3389/fgene.2022.856636. eCollection 2022.

Authors

Guilan Xie^{1

2}, Yan Zhang³, Wenfang Yang¹, Liren Yang^{1

2}, Ruiqi Wang^{1

2}, Mengmeng Xu¹, Landi Sun^{1

2}, Boxing Zhang^{1

2}, Xiaoyi Cui^{1

4}

Affiliations

¹ Department of Obstetrics and Gynecology, Maternal and Child Health Center, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² School of Public Health, Xi'an Jiaotong University Health Science Center, Xi'an, China.
³ Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁴ Peking University Health Science Center, Beijing, China.

Abstract

Objective: Microcephaly with pontine and cerebellar hypoplasia (MICPCH) is a rare X-linked dominant genetic disease, and most MICPCHs are ascribed to CASK mutations, while few are revealed in Chinese patients. This study aims to identify the pathogenic mutation in a Chinese proband with MICPCH. Methods: A 3-year-old female Chinese proband with MICPCH and her parents were included. Clinical data were collected from the medical records and recalled by the proband's mother. Whole genome sequencing and Sanger sequencing were used to find the pathogenic mutation of MICPCH. Results: The proband presented with postnatal progressive microcephaly, cerebellar hypoplasia, intellectual disability, motor and language development retardation and limb hypertonia. Genetic analysis indicated that there was a novel compound heterozygote nonsynonymous mutation, c.755T>C(p.Leu252Pro) in exon8 of CASK gene in the proband, but not in her parents. This CASK mutation has not been reported in other databases. Conclusion: This study broadens the mutation spectrum of the CASK gene and is of great value for precise prenatal diagnosis and genetic counseling.

Keywords: CASK gene; cerebellar hypoplasia; intellectual disability; microcephaly; whole exome sequencing.

Publication types

Case Reports