Analysis of a child with X-linked intellectual disability due to a maternal de novo splicing variant of the PAK3 gene.
10.3760/cma.j.cn5113874-20220513-00326
- Author:
Chen WANG
1
;
Xueping QIU
;
Hui HU
;
Bingyu JIN
;
Yating CHENG
;
Yue ZHAO
;
Chun ZHOU
;
Ling MA
;
Yuanzhen ZHANG
;
Fang ZHENG
Author Information
1. Center for Genetic Diagnosis & Department of Laboratory Medicine, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China. zhengfang@whu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Child;
Female;
Humans;
Male;
Pregnancy;
Exons;
Intellectual Disability/genetics*;
Mothers;
Mutation;
p21-Activated Kinases/genetics*;
Parents;
RNA Splicing
- From:
Chinese Journal of Medical Genetics
2023;40(7):865-870
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the genetic etiology for a child with profound intellectual disabilities and obvious behavioral abnormalities.
METHODS:A male child who had presented at the Zhongnan Hospital of Wuhan University on December 2, 2020 was selected as the study subject. Peripheral blood samples of the child and his parents were collected and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing. Short tandem repeat (STR) analysis was carried out to determine its parental origin. The splicing variant was also validated in vitro with a minigene assay.
RESULTS:WES results revealed that the child had harbored a novel splicing variant of c.176-2A>G in the PAK3 gene, which was inherited from his mother. The results of minigene assay have confirmed aberrant splicing of exon 2. According to the guidelines from the American College of Medical Genetics and Genomics, it was classified as a pathogenic variant (PVS1+PM2_Supporting+PP3).
CONCLUSION:The novel splicing variant c.176-2A>G of the PAK3 gene probably underlay the disorder in this child. Above finding has expanded the variation spectrum of the PAK3 gene and provided a basis for genetic counseling and prenatal diagnosis for this family.
