Genetic analysis of two novel variants in a Chinese pedigree affected with intellectual disorder
10.3760/cma.j.cn511374-20240709-00381
- VernacularTitle:智力障碍一个家系中两个新发变异的遗传学分析
- Author:
Xiaoxiao LYU
1
;
Chenyang XU
1
;
Yunzhi XU
1
;
Yanbao XIANG
1
Author Information
1. 温州市中心医院检验科 温州市精准医疗重点实验室，温州 325000
- Publication Type:Journal Article
- Keywords:
Intellectual disability;
TRIP12 gene;
GRIN2B gene;
Whole exome sequencing;
Pedigree
- From:
Chinese Journal of Medical Genetics
2024;41(12):1456-1462
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the clinical phenotype and genetic characteristics of two siblings with intellectual disability.Methods:Clinical data and peripheral blood samples were collected from the proband, his younger sister and parents whom had presented at Wenzhou Central Hospital in February 2024. Low-coverage massively parallel copy number variation sequencing (CNV-seq) and whole exome sequencing (WES) were carried out for the family. Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was performed on a fetus upon the couple′s subsequent pregnancy. The study was approved by the Medical Ethics Committee of Wenzhou Central Hospital(Ethic No.L2024-07-001).Results:The proband was a 12-year-old boy who had presented with mental retardation and language delay. His 10-year-old sister also manifested delayed mental and motor development. Whole exome sequencing revealed that the proband and his sister had respectively harbored a novel heterozygous c. 3549_3550del (p.Glu1183Aspfs*29) variant of the TRIP12 gene and a novel heterozygous c. 99del (p.Ser34Alafs*38) variant of the GRIN2B gene. Sanger sequencing confirmed that both variants had a de novo origin. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were classified as pathogenic (PVS1+ PS2_Supporting+ PM2_Supporting). Neither variant was found to be carried by the fetus upon prenatal diagnosis. Conclusion:Above variants probably underlay the mental disorders in the two siblings, and the concurrent occurrence of two novel pathogenic variants in a family has been extremely rare.
