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

BACKGROUND: Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid β-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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851016/
https://www.ncbi.nlm.nih.gov/pubmed/36683633
http://dx.doi.org/10.12998/wjcc.v10.i36.13426
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author 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
author_facet 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
author_sort Wen, Xiao-Ling
collection PubMed
description BACKGROUND: Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid β-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 the α2 and α3 helices of GBA1. 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. 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.
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spelling pubmed-98510162023-01-20 Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report 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 World J Clin Cases Case Report BACKGROUND: Gaucher disease (GD) is caused by a GBA1 gene mutation that leads to decreased acid β-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 the α2 and α3 helices of GBA1. 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. 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. Baishideng Publishing Group Inc 2022-12-26 2022-12-26 /pmc/articles/PMC9851016/ /pubmed/36683633 http://dx.doi.org/10.12998/wjcc.v10.i36.13426 Text en ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved. https://creativecommons.org/licenses/by-nc/4.0/This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
spellingShingle Case Report
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
Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report
title Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report
title_full Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report
title_fullStr Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report
title_full_unstemmed Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report
title_short Compound heterozygous p.L483P and p.S310G mutations in GBA1 cause type 1 adult Gaucher disease: A case report
title_sort compound heterozygous p.l483p and p.s310g mutations in gba1 cause type 1 adult gaucher disease: a case report
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851016/
https://www.ncbi.nlm.nih.gov/pubmed/36683633
http://dx.doi.org/10.12998/wjcc.v10.i36.13426
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