Clinical and genetic analysis of RARS2-related pontocerebellar hypoplasia
10.3760/cma.j.cn511374-20250217-00083
- VernacularTitle:RARS2相关脑桥小脑发育不良患儿6例的临床及遗传学分析
- Author:
Xiaoli ZHANG
1
;
Mengyue WANG
;
Jialin LI
;
Yichao MA
;
Junling WANG
;
Xiaoli LI
;
Rui HAN
;
Dan XU
;
Shuang JIN
;
Tianming JIA
;
Shujin LI
;
Xianjie HUANG
;
Yueqin LI
Author Information
1. 郑州大学第三附属医院儿科小儿神经内科，郑州 450052
- Publication Type:Journal Article
- Keywords:
RARS2 gene;
Pontocerebellar hypoplasia type 6;
Epilepsy;
Developmental delay
- From:
Chinese Journal of Medical Genetics
2025;42(9):1096-1105
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the clinical characteristics and genotypic changes of six children with RARS2 gene variants. Methods:The clinical data of 6 children with RARS2 gene variants diagnosed at the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2024 were collected. Genetic variants were detected using trio-whole exome sequencing. Genomic DNA was extracted from samples and subjected to high-throughput sequencing. Variants were detected and analyzed using relevant databases and software. Pathogenic variants were validated by Sanger sequencing. The protein structure encoded by a previously unreported variant was predicted using a SWISS-MODEL online server. This study was approved by the Medical Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethics No.: 2024-373-01). Results:Among the six children, four were males and two were females, with the most recent follow-up age ranging from 1-year-and-1-month to 7 years old. The age of onset was under 1 year in all cases. All six children exhibited seizures, including infantile spasms in three, spasms and tonic spasms in one, and focal seizures in two. One child became seizure-free for 4 ~ 5 years following Valproic acid combined with topiramate and adrenocorticotropic hormone (ACTH) pulse therapy, but subsequently experienced a relapse. Another child has remained seizure-free for nearly one year with oral sodium valproate, levetiracetam, and a " cocktail" therapy. Seizures were not controlled in the remaining four children. Pontocerebellar hypoplasia was observed on neuroimaging in two children. All six patients exhibited severe psychomotor retardation. A total of 10 RARS2 gene variants were identified, three of which were previously unreported. Conclusion:The predominant clinical features of Pontocerebellar hypoplasia associated with RARS2 gene variants include infantile onset, severe psychomotor retardation or regression, drug-resistant epilepsy, and feeding difficulties. The characteristic neuroimaging finding is pontocerebellar hypoplasia. However, its appearance may vary widely with time. The majority of affected children have a poor prognosis.
