Beta-glucocerebrosidase gene mutation in a sample of Egyptian patients with Gaucher disease

Fateen, Ekram M.; Fathy, Heba M.; Abd El-Fattah, Abeer I.; Soliman, Hala N.; Elbagoury, Nagham M.; Essawi, Mona L.

doi:10.4103/MXE.MXE_22_19

Beta-glucocerebrosidase gene mutation in a sample of Egyptian patients with Gaucher disease

Authors

Abstract

Background
Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder resulting from inherited deficiency in the acid β-glucocerebrosidase enzyme (). This defective activity causes accumulation of glucocerebroside in the lysosomes of cells derived from the monocyte/macrophage lineage. Glucocerebrosidase-engorged cells, termed Gaucher cells, infiltrate various organs, leading to multisystem abnormalities. Three major clinical types are delineated by the absence (type I) or presence (types II and III) of primary central nervous system involvement.
Objective
Identification of mutations of the whole coding region of β-glucocerebrosidase () gene among 24 Egyptian patients with GD.
Patients and methods
In this study, molecular assessment was carried out by sequencing of 11 exons of the gene for the 24 studied patients from 24 families, their age ranged from 10 months to 10 years. Seventeen (70.8%) families out of 24 were with parental consanguinity.
Resulst
The disease-causing mutations were revealed in 16 patients. Eleven (45.8%) patients were homozygous for p.L483P mutation. Two (8.3%) patients were homozygous for p.N409S mutation. One (4.2%) patient showed a compound heterozygous for p.N409S/p.L483P mutation; one patient showed heterozygous p.L483P mutation while one patient showed homozygous p.R87W mutation (4.2%). The p.R87W mutation was not reported as one of the targeted mutations screening of all previous studies in Egyptian GD patients.
Conclusion
The study identified the most common mutation p.L483P followed by p.N409S located on exons 9 and 10, respectively. Interestingly, missense p.R87W mutation is the first time to be reported in Egyptian GD patients' genotype database using sequencing of the whole gene.

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