Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease:A case report  

作　　者：Xiao-Ling Wen Yao-Zi Wang Xia-Lin Zhang Jia-Qiang Tu Zhi-Juan Zhang Xia-Xia Liu Hai-Yan Lu Guo-Ping Hao Xiao-Huan Wang Lin-Hua Yang Rui-Juan Zhang 

机构地区：[1]Department of Hematology,The First People’s Hospital of Yibin,Yibin 644000,Sichuan Province,China [2]Department of Hematology,The Second Hospital of Shanxi Medical University,Taiyuan 030001,Shanxi Province,China [3]Department of Hematology,The Third Hospital of Shanxi Medical University,The Shanxi Bethune Hospital,The Shanxi Academy of Medical Sciences,The Tongji Shanxi Hospital,The Shanxi Medical University,Taiyuan 030032,Shanxi Province,China [4]Department of Hematology,The Children’s Hospital of Shanxi,Taiyuan 030006,Shanxi Province,China

出　　处：《World Journal of Clinical Cases》2022年第36期13426-13434,共9页世界临床病例杂志

基　　金：Supported by Shanxi Key Research and Development Project,No.201903D321133;Shanxi Bethune Hospital’s Talent Introduction Scientific Research Start-up Fund Project,No.2021RC038 and 2021RC017。

摘　　要：BACKGROUND Gaucher disease(GD)is caused by a GBA1 gene mutation that leads to decreased acidβ-glucosidase activity[glucocerebrosidase(GCase)].This study aimed to identify and characterise compound heterozygous mutations in GBA1 in a patient with type 1 GD.CASE SUMMARY Here,we report a rare adult-onset type 1 GD in a 46-year-old female patient with clinical manifestations of giant spleen,thrombocytopenia,and bone pain,diagnosed by enzymatic and genetic testing.Enzymology and whole exome sequencing revealed heterozygous missense mutations in exon 10 c.1448T>C(p.L483P)and exon 7 c.928A>G(p.S310G)of GBA1.The latter was first reported in patients with GD.Structural modelling showed that p.S310G and p.L483P were distant from the GCase active site.The p.S310G mutation in domain 1 may decrease stability between theα2 andα3 helices of GBA1.The p.L483P mutation in domain 2 reduced the van der Waals force of the side chain and disrupted the C-terminalβ-sheet.The patient was treated with imiglucerase replacement therapy,and her condition was stable.CONCLUSION The p.L483P/p.S310G novel compound heterozygous mutation underlies type 1 GD and likely affects GCase protein function.This is the first description of p.S310G being associated with mild type 1 GD in the context of a coinherited p.L483P mutation.

关 键 词：Gaucher disease Parkinson’s disease Lipid metabolism Molecular mechanism Case report 

分 类 号：R596[医药卫生—内科学]