Mutational Analysis and Genotype Investigation of Less Known Gaucher Mutations through Haplotype Analysis in Iranian Gaucher Patients

Gaucher's disease (GD) is the most frequent lysosomal storage disorder resulting from a deficiency of the enzyme glucocerebrosidase (GBA) which causes the accumulation of glucocerebroside. More than 500 mutations have been reported on the GBA gene so far. In this study, we aimed to investigate more on the genotype of less known mutations through haplotype analysis to explain their disease-causing inheritance. Eight patients and three carriers from nine different families were enrolled in the study. DNA sequencing of all GBA gene's exons was performed and pathogenicity of the mutations was investigated. Using GBA gene-linked STR markers, allele segregations were determined in some families. A total of six different mutations were determined. Five and three patients were identified to carry mutations in homozygous and compound heterozygote patterns respectively, three participants also were identified as carriers. The most prevalent mutations were c.1448 T > C and RecNcil, however, three less common mutations were identified (i.e., c.1223 C > T, c.1315 A > G, and c.1214 G > C). In conclusion, we evaluated six different mutations in Iranian patients and elucidated the inheritance of the three less-known mutations by linkage analysis.