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

• Published in: 中华医学杂志：英文版 2016 (9), p.1072-1077
• Main Author: Lin-Yu Liu Fei Liu Si-Chen Du Sha-Yi Jiang Hui-Jun Wang Jin Zhang Wei Wang Duan Ma
• Format: Article
• Language: English
• Subjects: GBA; 基因组DNA; 外周血白细胞; 序列比对; 突变型; 结构预测; 葡萄糖苷酶; 隐性遗传病
• ISSN: 0366-6999; 2542-5641

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.