Gaucher Disease: Identification and Novel Variants in Mexican and Spanish Patients
| Autor: | Pilar Giraldo Castellano, Laura López de Frutos, José Elias García Ortiz, Elsa Avila Arreguin, Raúl Silva Garcia, Sergio Franco Ornelas, Cecilia Correa González, Francisco Blanco Favela |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Genetics Gaucher Disease Genotype Chromosome General Medicine Disease Glucocerebroside Biology Spanish population 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Mutation Humans In patient Gene Glucocerebrosidase Alleles Genetic Association Studies |
| Zdroj: | Archives of Medical Research. 52:731-737 |
| ISSN: | 0188-4409 |
| Popis: | Background Gaucher disease (GD) is the most prevalent lysosomal storage disorder, affecting all ethnic groups, although its prevalence is higher in Ashkenazi Jewish populations. Three clinical forms of GD have been described: Type 1 non-neuronopathic, type 2 acute neuronopathic, and type 3 subacute neuronopathic. An autosomal recessive disorder is caused by variants in the human glucocerebrosidase gene (GBA; MIM*606463) located on chromosome 1q21, resulting from deficit or lack of activity of the β-glucocerebrosidase enzyme, leading to the accumulation of glucocerebroside substrate in the cells of the macrophage-monocyte system. The aim was to determine variants in Mexican and Spanish populations with GD. Methods We report the molecular analysis by a direct automatic method sequenced of both chains of the GBA gene, in 69 Mexican and 369 Spanish patients with GD. Results We detected 75 variants with pathogenic or likely pathogenic effect and, identified 3 new variants c.408_412del/p.Asn136Lysfs*15; c.820G>A/p.Glu274Lys and c.1058T>G/p*. The most frequent variants were c.1448T>C/p.Leu483Pro/L444P and c.1226A>G/p.Asn409Ser/N370S. The detected genotypes were compared with data from both GD registries to define similarities and differences in both populations. Conclusions We defined the variant profile in patients with GD in a Mexican and a Spanish population and compared them. The screening permitted the detection of common variants and the report of three new variants, in addition to a variant associated with Parkinson disease but not with GD. Since molecular diagnosis has considerable predictive value in GD, it is important to study the genotype-phenotype correlations, establishing the severity of the variant. |
| Databáze: | OpenAIRE |
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