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

Gaucher disease (GD, ORPHA355) is a rare autosomal recessive genetic disease caused by mutations in , 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 . Bioinformatics analysis suggested that the two mutations are pathogenic. Functional studies showed that mRNA and GCase protein levels of mutant types were significantly less than the wild-type. In the cell lysates, the two mutations of 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.