Genetic analysis of a pedigree affected with Intellectual disability due to variants of two different genes
10.3760/cma.j.cn511374-20240426-00257
- VernacularTitle:两种基因变异所致智力障碍一个家系的遗传学分析
- Author:
Tingting SHI
1
;
Zengguo REN
;
Ke YANG
;
Litao QIN
;
Xingxing LEI
;
Bing ZHANG
;
Shixiu LIAO
;
Li WANG
Author Information
1. 郑州大学人民医院，河南省人民医院，医学遗传研究所，郑州 450003
- Keywords:
Intellectual disability;
RNF13 gene;
UBE3A gene;
Whole exome sequencing
- From:
Chinese Journal of Medical Genetics
2024;41(11):1302-1307
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the genetic etiology of a pedigree with intellectual disability and explore its pathogenesis.Methods:A Chinese pedigree which had presented at the Henan Provincial People′s Hospital in March 2023 was selected as the study subject. Clinical data of the pedigree were collected, along with peripheral venous blood samples from its members. Whole exome sequencing (WES) was carried out, and candidate variants were verified by Sanger sequencing. Amniotic fluid was collected for prenatal diagnosis. This study was approved by the Medical Ethics Committee of the Henan Provincial People′s Hospital (No. 2019-134).Results:Both the proband (a 6-year-old male) and his mother (30 years old) had various degrees of intellectual and motor impairment. WES revealed that the proband has harbored a de novo heterozygous c. 2563_2567dup (p.Lys856fs) variant of the UBE3A gene, while his mother, maternal grandmother and fetus had all harbored a novel heterozygous c. 409+ 1G>A variant of the RNF13 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+ PS1+ PM2_Supporting; PVS1+ PM2_Supporting+ PP3). Conclusion:Based on the clinical manifestations and the result of genetic testing, the heterozygous c.2563_2567dup (p.Lys856fs) variant of the UBE3A gene probably underlay the intellectual disability and developmental delay in the proband, whilst the heterozygous c. 409+ 1G>A variant of the RNF13 gene may underlie the intellectual disability in the proband′s mother and grandmother. Above results have enabled genetic counseling and prenatal diagnosis for this pedigree.
