Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8648079 | Blood Cells, Molecules, and Diseases | 2018 | 5 Pages |
Abstract
Gaucher disease (GD) is a common lysosomal storage disorder caused by the deficiency of acid β-glucosidase, due to mutations in the GBA gene. To explore the clinical and molecular characteristics of GD patients from Southern China, GBA gene were analyzed by nest PCR and direct Sanger-sequencing. Novel missense mutations were transiently transfected in COS-7 cells by plasmid system for functional verification. Among the 22 GD patients, 19 patients were classified as type 1 and three as type 2. Over 60% of the type 1 patient had the onset before two years of age and about 42% of them died before three years of age. Six type 1 patients with L444P homozygous genotype, presented with early onset and severe hepatosplenomegaly. Four novel mutations Y22C, F109L, L149F and c.983_990delCCCACTGG were identified. The GBA activities in vitro of novel mutants Y22C, F109L and L149F were 20.2%, 6.9% and 6.5% of the wild-type, respectively. L444P mutation accounted for 47.7% of the mutant alleles. Our results revealed that type 1 GD tends to present with a severe phenotype among southern Chinese. L444P was the most prevalent mutation and L444P homozygous genotype was associated with severe type 1 GD. Three novel missense mutations identified were pathogenic.
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Authors
Yuyu Feng, Yonglan Huang, Chengfang Tang, Hao Hu, Xiaoyuan Zhao, Huiying Sheng, Wen Zhang, Minyi Tan, Ting Xie, Jipeng Zheng, Zongcai Liu, Xueying Su, Yongxian Shao, Xiuzhen Li, Jing Cheng, Xiaojian Mao, Li Liu,