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Blood Cells Mol Dis. 2018 Feb;68:30-34. doi: 10.1016/j.bcmd.2016.10.026. Epub 2016 Nov 3.

Clinical and molecular characteristics of patients with Gaucher disease in Southern China.

Author information

1
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
2
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China. Electronic address: xxhuang321@163.com.
3
Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China. Electronic address: liliuxia@hotmail.com.

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.

KEYWORDS:

Expression study; GBA gene; Gaucher disease; Molecular analysis

PMID:
27865684
DOI:
10.1016/j.bcmd.2016.10.026
[Indexed for MEDLINE]

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