Journal Article

The loss of function GBA1 c.231C > G mutation associated with Parkinson disease

Zheng, Yingchun, Xiong, Fu, Su, Quanxi, Zhang, Jian, Huang, Yuanbing, Zhang, Guilian, Zheng, Boyang, Chen, Dejie

2023

Overview

Parkinson’s disease (PD) is the second most common neurodegenerative disease characterized by bradykinesia, rigidity, and tremor. However, familial PD caused by single-gene mutations remain relatively rare. Herein, we described a Chinese family affected by PD, which associated with a missense heterozygous glucocerebrosidase 1 (GBA1) mutation (c.231C > G). Clinical data on the proband and her family members were collected. Brain MRI showed no difference between affected and unaffected family members. Whole-exome sequencing (WES) was performed to identify the pathogenic mutation. WES revealed that the proband carried a missense mutation (c.231C > G) in GBA1 gene, which was considered to be associated with PD in this family. Sanger sequencing and co-segregation analyses were used to validate the mutation. Bioinformatics analysis indicated that the mutation was predicted to be damaging. In vitro functional analyses were performed to investigated the mutant gene. A decrease in mRNA and protein expression was observed in HEK293T cells transfected with mutant plasmids. The GBA1 c.231C > G mutation caused a decreased GBA1 concentration and enzyme activity. In conclusion, a loss of function mutation (c.231C > G) in GBA1 was identified in a Chinese PD family and was confirmed to be pathogenic through functional studies. This study help the family members understand the disease progression and provide a new example for studying the pathogenesis of GBA1-associated Parkinson disease.

• Publisher: Springer Vienna,Springer Nature B.V
• Subject: Bioinformatics / Disease progression / Enzymatic activity / Enzymes / Families & family life / Gene expression / Genomes / Glucosylceramidase / Medicine / Medicine & Public Health / Missense mutation / Movement disorders / mRNA / Mutants / Mutation / Neurodegenerative diseases / Neurology / Neurology and Preclinical Neurological Studies - Original Article / Neurosciences / Parkinson's disease / Pathogenesis / Plasmids / Point mutation / Proteins / Psychiatry / Reagents / Tremor / Whole genome sequencing