Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene.
10.3760/cma.j.cn511374-20220517-00333
- Author:
Jinghan XU
1
;
Jingjing LI
;
Zhihui JIAO
;
Gege SUN
;
Duo CHEN
;
Xiangdong KONG
;
Li WANG
Author Information
1. Genetic and Prenatal Diagnosis Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. fccwangl56@zzu.edu.cn.
- Publication Type:Journal Article
- MeSH:
Humans;
Intellectual Disability/genetics*;
Genetic Testing;
Phenotype;
Exome Sequencing;
Heterozygote;
Mutation;
Chromosomal Proteins, Non-Histone/genetics*;
Phosphoproteins/genetics*
- From:
Chinese Journal of Medical Genetics
2023;40(1):47-52
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene.
METHODS:Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants.
RESULTS:The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin.
CONCLUSION:The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.
