Özet:

Gaucher disease, the most prevalent lysosomal storage disease and transmitted as an autosomal recessive trait results from an inherited deficiency in the enzyme glucocerebrosidase. The enzyme substrate glucocerebroside accumulate in the patient’s spleen, liver and bone marrow. The resultant accumulation in several tissues and organs leads to numerous manifestations like anemia, hepatosplenomegaly, thrombocytopenia, growth retardation and skeletal disease. Three clinical forms of Gaucher disease have been described: Type 1 non-neuronopathic, Type 2 acute neuronopathic, and Type 3 subacute neuronopathic. The gene responsible for glucocerebrosidase is GBA, located on chromosome lq21. There are 11 exon and 10 introns are present in the gene. The exon 9 and 10 is the hot spot exon of said disease in Asia and also reported in worldwide. The current study was about on exon 10 because its most common exon. In current study, 7 families were involved for sequencing and molecular analysis. For sequencing, genomic DNA extraction was done by the phenol- chloroform method and PCR reaction were done. Sequencing of 7 patients revealed 12 different variants including 5 polymorphisms (Homo/hetero). 3 variants out of these 5 were nonsynonymous. The other 7 variants were predicted to be disease causing mutation by mutation taster. 4 out of 7 mutations were non-synonymous, while 3 were synonymous. 6 novel mutations were found, 02 of them were homozygous and 04 are heterozygous mutations, and one already reported mutation c.1152G>A with rs12747811. While we found 4 novel polymorphisms, 02 heterozygous and 02 homozygous polymorphisms and one of them was already reported polymorphism that is chr1:155205170A>G having rs143255568. This shows comprehensive picture of molecular properties of GBA gene and related phenotypic variations in the patients. We need further evaluation of remaining exons in order to determine the carrier ratio of Gaucher disease in our population or whether we should screen our neonates for such lysosomal disorders.

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