Compound heterozygous mutations in POLR3A gene cause global developmental delay with epilepsy and striatal degeneration
10.3760/cma.j.cn113694-20210322-00208
- VernacularTitle:POLR3A基因复合杂合突变导致全面发育落后合并癫痫、纹状体变性
- Author:
Fang HE
1
;
Leilei MAO
;
Nan PANG
;
Fei YIN
;
Jing PENG
;
Li YANG
Author Information
1. 中南大学湘雅医院儿科，湖南省儿童智力障碍研究中心，长沙 410008
- Keywords:
POLR3A gene;
Mutation;
Global developmental delay;
Epilepsy;
Striatal degeneration
- From:
Chinese Journal of Neurology
2021;54(12):1282-1289
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the clinical, imaging and genetic features of patients with global developmental delay combined with epilepsy and striatal degeneration caused by POLR3A gene mutations.Methods:A total of three patients from two families with non-consanguineous marriages admitted to the Department of Pediatric Neurology of Xiangya Hospital of Central South University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole-exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:All three patients presented with global developmental delay, seizures, dystonia. Head magnetic resonance imaging of all patients suggested basal ganglia atrophy and striatal degeneration. All had compound heterozygous mutations of c.1980 G>C; c.1771-6 C>G and c.2044C>T; c.1771-7 C>G in POLR3A gene as indicated by whole-exome sequencing. Sanger sequencing validation confirmed that the compound heterozygous mutations were originated from the parents of probands from the two families, respectively. Bioinformatic analysis suggested pathogenic features of the mutations.Conclusions:Compound heterozygous mutations in POLR3A gene , including a splice site mutation result in global developmental delay combined with epilepsy, striatal degeneration. Clinicians should promote the awareness of POLR3 related spectrum disorders, thus make early recognition and diagnosis.
