الفهرس 
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Abstract
Gaucher disease is the most prevalent lysosomal storage diseases which results from inherited deficiency in the GBA gene. The present study aimed to screen for eight of the most common mutations (IVS2+1G>A, 84GG, P266L, N370S, V394L, D409H, R496H and L444P) among Egyptian GD study group patients. The study included 34 GD patients referred from various regions of Egypt .Patients were diagnosed by the biochemical genetics department, National Research Centre (NRC), Cairo, Egypt. After diagnosis a blood sample on EDTA was provided for mutation analysis. Genomic DNA was extracted using standard procedure and then amplified. For each of the mutations P266L, N370S, V394L, D409H, L444P and R496H, the amplified fragments were digested with the specific restriction endonucleases. Sanger sequencing of exon 2, encompassing the two remaining mutations IVS2+1G>A and 84GG was the method of choice as the restriction endonuclease result was inconclusive. Enzyme levels of patients displayed marked reduction of β- glucocerebrosidase activity (0.5364±0.21) and marked elevation of chitotriosidase activity ranging from 133 to 25718 µ mol/l/h .The most common genotype was the heterozygous IVS2+1G>A/- in 16 patients (47%) followed by homozygous L444P; found in 13 patients (38.2%). Homozygous N370S was detected in two siblings with frequency of (5.8 %). Compound heterozygous L444P/IVS2+1G>A was detected in two patients with a frequency of (5.8%). One patient is still with unknown mutation on both alleles till now. All the remaining
84 mutations, 84GG, P266L, V394L, D409H, and R496H were not found in any of the study group patients. The most frequent allele in patients was L444P which had a frequency of (41.2%). The IVS2+1G>A allele had a frequency of (26.5%) and N370S allele had a frequency of (5.8%). Undetected alleles had a frequency of (26.5%). In addition, the highest number of alleles was found in the Delta region (82.4%) compared to the Upper Egypt region (17.6%). Concerning Genotype frequency in different types of GD patients, 16 patients (48.5%) had type I, one patient (3%) had type II and 16 patients (48.5%) had type III GD. To conclude, most common allele among Egyptian GD patients is L444P (41.2%) and patients homozygous for L444P equal to (38.2%).This explains the high incidence of the neurologic form of GD among Egyptian patients (51.5%).