Wen Xiao-Ling, Wang Yao-Zi, Zhang Xia-Lin, Tu Jia-Qiang, Zhang Zhi-Juan, Liu Xia-Xia, Lu Hai-Yan, Hao Guo-Ping, Wang Xiao-Huan, Yang Lin-Hua, Zhang Rui-Juan
Department of Hematology, The First People's Hospital of Yibin, Yibin 644000, Sichuan Province, China.
Department of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China.
World J Clin Cases. 2022 Dec 26;10(36):13426-13434. doi: 10.12998/wjcc.v10.i36.13426.
Gaucher disease (GD) is caused by a gene mutation that leads to decreased acid β-glucosidase activity [glucocerebrosidase (GCase)]. This study aimed to identify and characterise compound heterozygous mutations in in a patient with type 1 GD.
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 . 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 the α2 and α3 helices of . The p.L483P mutation in domain 2 reduced the van der Waals force of the side chain and disrupted the C-terminal β-sheet. The patient was treated with imiglucerase replacement therapy, and her condition was stable.
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.
戈谢病（GD）由基因突变引起，该突变导致酸性β-葡萄糖苷酶活性[葡糖脑苷脂酶（GCase）]降低。本研究旨在鉴定和表征1型GD患者中的复合杂合突变。
在此，我们报告了一名46岁女性患者罕见的成人起病1型GD，其临床表现为巨脾、血小板减少和骨痛，通过酶学和基因检测确诊。酶学和全外显子组测序显示，GBA基因外显子10的c.1448T>C（p.L483P）和外显子7的c.928A>G（p.S310G）存在杂合错义突变。后者首次在GD患者中报道。结构建模显示，p.S310G和p.L483P与GCase活性位点距离较远。结构域1中的p.S310G突变可能会降低GBA的α2和α3螺旋之间的稳定性。结构域2中的p.L483P突变降低了侧链的范德华力并破坏了C端β折叠。该患者接受了伊米苷酶替代治疗，病情稳定。
p.L483P/p.S310G新型复合杂合突变是1型GD的基础，可能影响GCase蛋白功能。这是首次描述在共遗传的p.L483P突变背景下，p.S310G与轻度1型GD相关。
