Spectrum of GBA mutations in patients with Gaucher disease from Slovakia: identification of five novel mutations.

BACKGROUND

Gaucher disease is the most common lysosomal storage disorder and is caused by a deficiency of the enzyme glucocerebrosidase. Enzyme deficiency leads to the accumulation of undegraded substrates, mainly in cells of the monocyte/ macrophage lineage, which is responsible for the clinical manifestations of the disease. To date, no study has attempted to identify the mutation spectrum of the glucocerebrosidase gene (GBA) in Slovak patients

OBJECTIVES

To identify mutations in 14 Slovak patients with confirmed glucocerebrosidase deficiency.

METHODS

Using molecular genetics methods PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and direct sequencing of coding region GBA we identified the spectrum of mutations in our patients.

RESULTS

Five mutations (N370S, L444P, G377S, D409H and RecNciI) accounted for 75% of the mutant alleles. The remaining 25% were rare and probably individual mutations.

CONCLUSIONS

The mutational spectrum in our patients is similar to that observed in other European countries and corresponds to a Caucasian population, with N370S, L444P, RecNciI being the most common. Interestingly, mutation G377S was more frequent in our patients as compared to other published data. The C4W, L96P, H311N, 745delG and 1127_1128delTT mutations are described here for the first time in Gaucher disease, contributing to the panel of published GBA mutations.