Background: Gaucher's disease (GD) is an autosomal recessive disorder caused by a deficiency of acid beta-glucosidase (glucocerebrosidase [GBA]) that results in the accumulation of glucocerebroside within macrophages. Many mutations have been reported to be associated with this disorder. This study aimed to discover more mutations and provide data for the genetic pattern of the gene, which will help the development of quick and accurate genetic diagnostic tools for this disease. Methods: Genomic DNA was obtained from peripheral blood leukocytes of the patient and Sanger sequencing is used to sequence GBA gene. Sequence alignments of mammalian beta-GBA (GCase) and three-dimensional protein structure prediction of the mutation were made. A construct of this mutant and its compound heterozygous counterpart were used to measure GCase in vitro. Results: GCase is relatively conserved at p.T219A. This novel mutation differs from its wild-type in structure. Moreover, it also causes a reduction in GCase enzyme activity. Conclusion: This novel mutation (c.655A>G, p.T219A) is a pathogenic missense mutation, which contributes to GD.
[1]Fudan Univ, Dept Biochem & Mol Biol, Key Lab Metab & Mol Med, Minist Educ,Sch Basic Med Sci,Inst Med Sci, Shanghai 200032, Peoples R China.
[2]Shanghai Jiao Tong Univ, Shanghai Inst Med Genet, Shanghai Childrens Hosp, Shanghai 200032, Peoples R China.
[3]Fudan Univ, Inst Pediat, Childrens Hosp, Shanghai 200032, Peoples R China.
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