ABSTRACT
More than 200 mutations have been described in patients with Gaucher disease [GD] and usually more than one mutation achieves a high population frequency. Genotype I phenotype correlation in patients with GD are not established. This study was designed to determine the underlying mutations in Egyptian children with GD and to assess their relation to disease phenotype. The study comprised 17 children with GD, 13 males and 4 females with mean age 6,09 +/- 441 years in addition to 10 healthy controls with matched age and sex. Patients included 13 children with type 1, 2 children with type 2 and 2 with type 3 GD. DNA was extracted from peripheral blood leukocytes; exon 9 and 10 were amplified by PCR using specific primers and DNA sequences were determined by ABI 310 genetic analyzer. Wild type allele was detected in 95%of controls [19/20] and a normal variant in 1/20 [5%]. L444P allele was encountered in 50%of the alleles in type 1 patients [13/26], H451 P in 2/26 [7.7%] and recombinant alleles [RecNcil, RecNcil+M450L RecFs, RecFs+M450L] in 9/26 [34.6%]. L444P and Rec alleles each occurs in 214 [50%] of type 2 and 3. A new mutation has been described in this study [g.7336A>C, [M450L]] and 2 mutant alleles have not been determined. Genotypes in type 1 patients comprised; L444P/L444P [23,1%], Rec alleles/L444P [53.8%]. Type 2 and 3. patients had Rec alleles/L444P genotypes in all patients [100%]. There was no significant association between mutant alleles frequency [p=0.63] or genotype frequency [p=0.41] and disease phenotypes. L444P is the most frequent mutant allele followed by Rec alleles in studied patients. Novel mutations are continuosly detected adding more to this expanding panel of GD mutations. No significant genotype-phenotype association was observed in studied patients