Genetic analysis of a child with Charlevoix-Saguenay spastic ataxia due to variant of SACS gene.
10.3760/cma.j.cn511374-20220724-00489
- VernacularTitle:SACS基因变异所致Charlevoix-Saguenay型痉挛性共济失调患儿1例的遗传学分析
- Author:
Huan LUO
1
,
2
;
Xiaolu CHEN
;
Xueyi RAO
;
Yajun SHEN
;
Jinfeng LIU
;
Zuozhen YANG
;
Jing GAN
Author Information
1. Department of Pediatrics, West China Second University Hospital, Sichuan University
2. Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Key Laboratory of Development and Maternal and Child Diseases of Sichuan Province, Sichuan University, Chengdu, Sichuan 610041, China. cqs1950@163.com.
- Publication Type:Journal Article
- MeSH:
Female;
Humans;
Heat-Shock Proteins/genetics*;
Muscle Spasticity/genetics*;
Mutation;
Spinocerebellar Ataxias/pathology*;
Child, Preschool
- From:
Chinese Journal of Medical Genetics
2023;40(5):558-562
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS).
METHODS:Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG).
RESULTS:The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases.
CONCLUSION:The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.
