Genetic and clinical analysis of two children with mental retardation and microcephaly due to a frameshifting variant of CASK gene
10.3760/cma.j.cn511374-20230620-00376
- VernacularTitle:CASK基因移码变异致智力障碍伴小头畸形2例患儿的临床与遗传学分析
- Author:
Sujuan LIU
1
;
Yingying WANG
;
Houyan HUANG
;
Ping XU
;
Ye JIANG
;
Taocheng ZHOU
Author Information
1. 安徽省儿童医院中医科，合肥 230051
- Keywords:
CASK gene;
Mental retardation;
Cerebellar hypoplasia;
Microcephaly
- From:
Chinese Journal of Medical Genetics
2024;41(9):1090-1095
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical and genetic characteristics of two children with mental retardation and microcephaly.Methods: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. This study was approved by the Anhui Children′s Hospital (Ethics No. EYLL-2018-008).Results: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.Pro157Profs*9) frameshifting variant of the CASK gene, whilst child 2 has harbored a c. 1259_1269delCTGAGAATAAC (p.Pro420fs*27) 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 and the Association for Molecular Pathology (ACMG-AMP), both variants were rated as pathogenic (PVS1+ PS2+ PP3). Conclusion:The de novo variants of the CASK gene probably underlay the pathogenesis of mental retardation and microcephaly in both children.
