title: Clinical and molecular characteristics of patients with Gaucher disease in Southern China.
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.
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Yuyu
authors.initials: Y
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Yonglan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Chengfang
authors.initials: C
authors.lastname: Tang
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Xiaoyuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Sheng
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Minyi
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Jipeng
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Zongcai
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Su
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Shao
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Department of Genetics and Endocrinology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, 510623 Guangzhou, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Mao
authors.affiliation: 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.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D044466:Asian People / Q000235:genetics; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002681:China / Q000453:epidemiology; D002522:Chlorocebus aethiops; D005260:Female; D005776:Gaucher Disease / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D005962:Glucosylceramidase / Q000737:chemistry / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D008958:Models, Molecular; D009154:Mutation; D020125:Mutation, Missense; D017354:Point Mutation; D011487:Protein Conformation; D055815:Young Adult
chemical_list: D005962:Glucosylceramidase
keywords: Expression study; GBA gene; Gaucher disease; Molecular analysis