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J Hum Genet. 2013 Sep;58(9):594-9. doi: 10.1038/jhg.2013.60. Epub 2013 May 30.

A common and two novel GBA mutations in Thai patients with Gaucher disease.

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1
1] Department of Botany, Faculty of Science, Chulalongkorn University, Bangkok, Thailand [2] Department of Pediatrics, Center of Excellence for Medical Genetics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Abstract

Gaucher disease (GD) is an autosomal recessive disorder caused by mutations in the glucocerebrosidase (GBA) gene, leading to a deficiency of lysosomal β-glucosidase and accumulation of glycosphingolipids in macrophages. We studied five Thai families with GD (four with GD type 1 and one with GD type 2). Using long-template PCR, PCR using specific primers for the functional gene, direct sequencing of all coding regions of GBA and restriction enzyme digestions, all 10 mutant alleles were successfully identified. The common c.1448T>C (p.L483P or L444P) mutation was identified in 60% of mutant alleles. Of the two patients homozygous for the p.L483P (L444P) mutation, one died from hepatic failure at age 16 years and the other died from sepsis at age 12 years. This p.L483P (L444P) mutation was found in four different haplotypes, suggesting that it was a recurrent mutation, not caused by a founder effect. Two novel mutations, a missense (c.1204T>C, p.Y402H), and a termination codon mutation (c.1609T>C, p.X537A) were found. Studies to determine the molecular pathomechanism of the p.X537A mutation, the first of its kind in this gene, showed that it decreased the amount of protein being expressed and the enzymatic activity, while it was still correctly localized.

PMID:
23719189
DOI:
10.1038/jhg.2013.60
[Indexed for MEDLINE]
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