Gaucher Disease: clinical phenotypes and GBA mutation spectrum in Kazakhstani patients
Keywords:
Gaucher disease, mutations, β-D-glucocerebrosidase, GBA geneAbstract
Background and Aim: Gaucher disease (GD) is a rare lysosomal storage disorder caused by mutations in the β-glucosidase (GBA1) gene, with more than 500 variants described. This study aimed to investigate the clinical features and spectrum of GBA1 mutations in Kazakhstani patients with GD.
Methods:
Medical records from the national referral center for GD in Kazakhstan were reviewed. Forty-five patients with confirmed GD were included. Diagnosis was based on reduced β-glucosidase, glucocerebrosidase, and plasma chitotriosidase activity. The entire coding region of GBA1 was analyzed using bidirectional Sanger sequencing.
Results:
Among 45 patients from 38 unrelated families, 15 mutations were identified in 20 combinations, including 12 missense, 2 nonsense, 1 frameshift, 1 splice-site, and 1 recombinant mutation. Of the missense variants, 10 were pathogenic, while 2 novel variants (A316L and F477R) were classified as likely pathogenic. The most frequent mutations were L444P (62.2%) and N370S (42.2%). N370S predominated in type 1 GD (68%, p < 0.001), whereas L444P occurred in both type 1 (50%) and type 3 (85%).
Conclusions:
This study shows that 63% of Kazakhstani GD patients present with type 1 disease, most frequently associated with N370S (68%), while types 2 and 3 with neurological involvement account for 38%, predominantly linked to L444P (50% and 85%). These findings highlight the genetic and phenotypic heterogeneity of GD in Kazakhstan and provide the first detailed description of its molecular spectrum in this population.
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