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?-Glucan fragmentation by microfluidization and TNF-?-immunostimulating activity of fragmented ?-glucans
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Document Title
?-Glucan fragmentation by microfluidization and TNF-?-immunostimulating activity of fragmented ?-glucans
Author
Nanta P., Buachan P., Pinket W., Srinuanchai W., Pongwan P., Sramala I., Jarussophon S., Prathumpai W., Taweechotipatr M., Ruktanonchai U.R., Kasemwong K.
Affiliations
Department of Biochemistry, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkoknoi, Bangkok, Thailand; National Biobank of Thailand, National Science and Technology Development Agency, PathumThani, Khlong Luang, 12120, Thailand; Department of Ophthalmology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Thailand
Type
Article
Source Title
Journal of Health Research
ISSN
8574421
Year
2024
Volume
38
Issue
3
Page
240-250
Open Access
All Open Access, Gold
Publisher
College of Public Health Sciences, Chulalongkorn University
DOI
10.56808/2586-940X.1079
Abstract
Background: Leber's hereditary optic neuropathy (LHON) is a prevalent mitochondrial disease that is predominantly caused by mitochondrial (mtDNA) mutations. However, not all siblings with identical LHON mutations develop visual impairment, suggesting the influence of nuclear genetic variants. This study explores the role of these variants in LHON expression among siblings and relatives with the same maternal LHON mutations. Methods: A family with a homoplasmic G11778A mutation displaying significant LHON penetrance (50 % in female carriers) was examined. Exome sequencing was performed on four members (two affected, two unaffected). Detected variations were predicted using a Variant Effect Predictor (VEP) with a dbNSFP (database for nonsynonymous single nucleotide polymorphisms' functional predictions) plugin. Candidate variants were chosen based on their scores and LHON-related gene variations. Sanger sequencing was used for validation of 15 family members. Results: Exome analysis identified nine potential variations across eight genes. However, only the MSTO1 c.692 693delCC mutation showed a significant linkage to LHON expression in both additive (adj. p-value = 0.04) and dominant models (adj. p-value = 0.0112). This rare variant, located at the cleavage and polyadenylation site of the MSTO1 gene, could disrupt transcriptional termination, and thus alter MSTO1 gene expression. Conclusions: Given the role of the MSTO1 gene in controlling mitochondrial morphology, the MSTO1 c.692 693delCC mutation might instigate mitochondrial dysfunction. Thus, the MSTO1 gene is potentially a novel nuclear modifier for LHON. These findings pave the way for further research into the underlying mechanisms of LHON. ? 2024 The Authors.
License
CC BY
Rights
Authors
Publication Source
WoS