A Novel Functional Missense Mutation p.T219A in Type Gaucher＇s Disease  

作　　者：Lin-Yu Liu Fei Liu Si-Chen Du Sha-Yi Jiang Hui-Jun Wang Jin Zhang Wei Wang Duan Ma 

机构地区：[1]Department of Biochemistry and Molecular Biology, Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Institute of Medical Sciences, Fudan University, Shanghai 200032, China [2]Shanghai Institute of Medical Genetics, Children's Hospital of Shanghai, Shanghai Jiaotong University, Shanghai 200032, China [3]institute oi Pediatrics, Children's I~ospital Of Fudan 'University, Shanghai 2000321,China

出　　处：《Chinese Medical Journal》2016年第9期1072-1077,共6页中华医学杂志（英文版）

基　　金：This study was supported by grants from Natural Science Foundation of China （No. 81371269） and Shanghai Research Program （No. 14140902600, No. 2013ZYJB0015, and No. 14DJ 1400103）.

摘　　要：Background： Gaucher＇s disease （GD） is an autosomal recessive disorder caused by a deficiency of acid β-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 β-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.Background： Gaucher＇s disease （GD） is an autosomal recessive disorder caused by a deficiency of acid β-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 β-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.

关 键 词：Gaucher＇s Disease GCase GENETICS Novel Missense Mutation 

分 类 号：Q939.506[生物学—微生物学] Q781