Liu Sujuan, Wang Yingying, Huang Houyan, Xu Ping, Jiang Ye, Zhou Taocheng
Department of Traditional Chinese Medicine, Anhui Children's Hospital, Hefei, Anhui 230051, China.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2024 Sep 10;41(9):1090-1095. doi: 10.3760/cma.j.cn511374-20230620-00376.
To explore the clinical and genetic characteristics of two children with mental retardation and microcephaly.
Two children who had visited the Anhui Children's Hospital respectively on March 12 and June 22, 2021 were selected as the study subjects. Peripheral venous blood samples were collected from them and their parents, and subjected to chromosomal karyotyping and whole exome sequencing analyses. Candidate variants were verified by Sanger sequencing and pathogenicity analysis.
Chromosomal karyotyping and copy number detection of the two children had found no abnormality. Whole exome sequencing revealed that child 1 has harbored a c.471delT (p.Pro157Profs9) frameshifting variant of the CASK gene, whilst child 2 has harbored a c.1259_1269delCTGAGAATAAC (p.Pro420fs27) frameshifting variant of the CASK gene. Sanger sequencing confirmed that both variants were de novo in origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP), both variants were rated as pathogenic (PVS1+PS2+PP3).
The de novo variants of the CASK gene probably underlay the pathogenesis of mental retardation and microcephaly in both children.
