The molecular mechanism of Gaucher disease caused by compound heterozygous mutations in GBA1 gene

Qi Liu; Zongrui Shen; Hong Pan; Shunfei Ma; Fu Xiong; Fei He

doi:10.3389/fped.2023.1092645

The molecular mechanism of Gaucher disease caused by compound heterozygous mutations in GBA1 gene

Front Pediatr. 2023 Jan 26:11:1092645. doi: 10.3389/fped.2023.1092645. eCollection 2023.

Authors

Qi Liu¹, Zongrui Shen^{2

3}, Hong Pan⁴, Shunfei Ma^{2

3}, Fu Xiong^{2

3}, Fei He^{2

3}

Affiliations

¹ Department of Transfusion, Shaoxing People's Hospital, Shaoxing, China.
² Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.
³ Experimental Education/Administration Center, School of Basic Medical Science, Southern Medical University, Guangzhou, China.
⁴ Department of Hematology, Shaoxing People's Hospital, Shaoxing, China.

Abstract

Gaucher disease (GD, ORPHA355) is a rare autosomal recessive genetic disease caused by mutations in GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase). Here, we report a patient with GD who carried the heterozygous c.1240G > C (p.Val414Leu) mutation and the heterozygous pathogenic c.1342G > C (p.Asp448His) mutation in GBA1. Bioinformatics analysis suggested that the two mutations are pathogenic. Functional studies showed that GBA1 mRNA and GCase protein levels of mutant types were significantly less than the wild-type. In the cell lysates, the two mutations of GBA1 c.1240G > C and c.1342G > C caused a decreased GCase concentration, while the two mutations did not change the distribution in the cell. The pathogenicity of the compound heterozygous mutations was verified. Early diagnosis and treatment can improve the quality of life and prevent unnecessary procedures in patients with GD.

Keywords: GBA1; Gaucher disease; c.1240G > C; c.1342G > C; cell experiment.

Grants and funding

The work was supported by the National Key S&T Special Projects (grant no. 2021YFC100530), Department of Health of Zhejiang Province (grant no. 2021KY1137), National Natural Science Foundation of China (grant nos. 32170617, 31970558), Natural Science Foundation of Guangdong Province of China (grant no. 2022A1515012621).