Analysis of glucocerebrosidase (GBA) gene mutations in Iranian patients with Gaucher disease.

OBJECTIVES

Gaucher disease (GD) is the most common autosomal recessive disorder of glycolipid storage. It results from mutations in the glucocerebrosidase () gene and leads to GBA deficiency. Different mutations are associated with different phenotypes in the three major types of GD.

MATERIALS AND METHODS

The spectrum of mutations in gene in 26 unrelated patients with GD from different Iranian populations was determined by DNA sequencing, polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), and amplification-refractory mutation system (ARMS) methods. An analysis was also performed for novel mutations.

RESULTS

Six new mutations were identified in this study. The newly detected mutations that could be theoretically harmful included p.I200T (c.599T>C), p.H312D (c.934C>G), p.L325S (c.974T>C), p.L393V (c.1177C>G), p.S439G (c.1315A>G), and p.M455R (c.1365G>A). Also, p.L483P, p.N409S, p.W420X, p.E379K, p.R398Q, p.N227S, p.R202Q, and p.D448H mutations were identified in the patients. Besides, two new complex mutations, namely, p.S439G/p.S439G+p.E379K/- and p.R202Q/p.R202Q+p.N227S/p.N227S, were detected. The most common mutation in the population was p.L483P with an allele frequency of 32.7%, followed by p.N409S (19.2%).

CONCLUSION

The present study detected six new mutations of gene among GD patients. Two mutations (p.L483P and p.N409S) were especially common among Iranians; this finding can be used in implementing screening programs and understanding the molecular basis of GD.