Gaucher disease: Identification and novel variants in Mexican and Spanish patients

Arch Med Res 2021 Jun 13;S0188-4409(21)00116-8. doi: 10.1016/j.arcmed.2021.05.001.

PMID: 34134921

Raúl Silva García, Laura López de Frutos, Elsa Ávila Arreguin

Highlights: Because molecular diagnosis has a high predictive value in GD, it's crucial to look into the genotype-phenotype correlations and determine the severity of the variant.

Abstract

Background: Gaucher disease (GD) is the most common lysosomal storage disorder, affecting people of all ethnic backgrounds, albeit it is more common in Ashkenazi Jewish communities. Three clinical forms of GD have been identified: Type 1 non-neuronopathic, type 2 acute neuronopathic, and type 3 subacute neuronopathic. Variants in the human glucocerebrosidase gene (GBA; MIM*606463) on chromosome 1q21 cause an autosomal recessive disorder characterized by a deficiency or absence of activity of the -glucocerebrosidase enzyme, resulting in the accumulation of glucocerebroside substrate in macrophage-monocyte system cells. The goal was to determine variants in Mexican and Spanish populations with GD.

Methods: We report on the molecular study of 69 Mexican and 369 Spanish patients with GD using a direct automated approach that sequenced both chains of the GBA gene.

Results: We discovered 75 pathogenic or probable pathogenic variants, as well as three novel variants: c.408 412del/p.Asn136Lysfs*15; c.820G>A/p.Glu274Lys; and c.1058T>G/p*. c.1448T>C/p.Leu483Pro/L444P and c.1226A>G/p.Asn409Ser/N370S were the most common variants. To characterize commonalities and differences in both groups, the identified genotypes were compared to data from both GD registries.

Conclusions: We compared and characterized the variant profile in GD patients from a Mexican and a Spanish community. The screening allowed for the detection of common variants as well as the discovery of three novel variants, including one linked to Parkinson's disease but not to GD. Because molecular diagnosis has a high predictive value in GD, it's crucial to look into the genotype-phenotype correlations and determine the severity of the variant.

Keywords: Gaucher disease, Lysosomal storage disease, Variants, β-glucocerebrosidase