Glucosidase acid beta gene mutations in Egyptian children with Gaucher disease and relation to disease phenotypes.

ABSTRACT

INTRODUCTION: More than 200 mutations have been found in patients with Gaucher disease (GD) and some mutations usually have a high frequency in certain populations. Genotype/phenotype correlation in patients with GD has not been established. This study was designed to determine underlying mutations in Egyptian children with GD and to assess their relation to disease phenotypes. METHODS: This study comprised 17 patients with GD and 10 healthy controls. Thirteen patients were type 1 GD, 2 type 2, and 2 type 3. DNA was extracted from peripheral blood leukocytes. Exons 9 and 10 were amplified by polymerase chain reaction, and deoxyribonucleic acid sequencing was done with an ABI 310 genetic analyzer. RESULTS: Wild type allele was detected in 95% (19/20) and a normal variant in 5% (1/20) of controls. L444P allele was encountered in 50% (13/26) of the alleles in type 1 patients, H451P in 7.7% (2/26) and recombinant alleles (RecNcil, RecNcil + M450L, RecFs, RecFs + M450L) in 34.6% (9/26). L444P and Rec alleles each occurred in 50% (2/4) of type 2 and 3 patients. A new mutation was seen in this study {g.7336A>C, (M450L)} and 2 mutant alleles were not determined. Type 1 GD patients had L444P/L444P genotype (23.1%) and Rec alleles/L444P (53.8%), while type 2 and 3 GD patients had Rec alleles/L444P genotypes (100%) with a poor phenotype/genotype correlation. CONCLUSIONS: L444P and Rec alleles are common in the studied patients. Novel mutations are continuously detected, adding to the expanding panel of GD mutations. No significant genotype-phenotype association was observed.