A Compound Heterozygous Pathogenic Variant in <i>B4GALNT1</i> Is Associated With Axonal Charcot-Marie-Tooth Disease

Hong, Ji Man; Jeon, Hong Jun; Choi, Young Chul; Cho, Hanna; Hong, Young Bin; Park, Hyung Jun

doi:10.3988/jcn.2021.17.4.534

Cited by 8 publications

(3 citation statements)

References 48 publications

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“…The change in expression or mutation B4GALNT1 has been associated with tumor progression in melanoma [9] by inducing of gangliosides GM2/GD2, clear cell renal cell carcinoma (ccRCC) [10], colorectal cancer [11], lung adenocarcinoma [12], oral squamous cell carcinoma [13], breast cancer [14] and cervical cancer [15]. Apart from cancer B4GALNT1 has been associated with Hereditary Spastic Paraplegia [16], Parkinson’s disease [17] and Axonal Charcot-Marie-Tooth Disease [18]. The aforementioned findings indicate the significance of B4GALNT1 as a crucial regulator in the progression of cancer.…”

Section: Introductionmentioning

confidence: 99%

Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis

Verma,

Lokhande,

Srivastava

et al. 2024

Preprint

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Liver hepatocellular carcinoma (LIHC) is one of the most frequent types of malignant cancer in the globe. The identification of new biomarkers for the LIHC is critical. We used TCGA-LIHC gene expression datasets for this study. Several feature selection methods were used to find the top gene signatures that distinguish LIHC cancer from normal samples. Eleven machine learning algorithms were used on these selected characteristics, and model performance evaluation revealed that Naive Bayes Classifiers (AUC = 0.965) performs the best for a selection of 55 protein coding genes. Among 55 protein coding genes we found B4GALNT1 (Beta-1,4-N-acetyl-galactosaminyltransferase 1) which is differentially regulated in LIHC. With several evidence B4GALNT1 plays crucial role in tumorigenesis in many cancers, therefore we conducted systematic bioinformatics approach with mutational and structural analysis of B4GALNT1 in LIHC. Moreover, survival analysis, immune cell infiltration, most significant associated methylated CpG probe and access the accuracy of B4GALNT1 conducted to find the potential role of B4GALNT1. The results suggested that B4GALNT1 was significantly expressed in most cancers including LIHC. Finally, 16 missense mutations identified through cBioportal, Cosmic Database, and Human Variant Database, among which 6 mutations (P64Q, S131F, A311S, R340Q, D478H, and P507Q) found to be deleterious when analysed by in-silico prediction algorithms such as SIFT, PolyPhen2, I Mutent2 and CADD in LIHC. Molecular Dynamics simulation analysis was performed to understand the atomic details of the structure and functional changes. Results from this study suggest the impact of these missense variants on the structure of the B4GALNT1 protein and its pathogenic relevance. Our study demonstrated that B4GALNT1 may be evaluated as a novel target for liver cancer therapy because it has been found to be overexpressed in Liver and correlates with a poor prognosis.

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Section: Introductionmentioning

confidence: 99%

Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis

Verma,

Lokhande,

Srivastava

et al. 2024

Preprint

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“…For example, loss of GM3 synthase (GM3S) leads to human autosomal recessive infantile‐onset symptomatic epilepsy syndrome and Rett syndrome‐like disorder (Lee et al, 2016; Simpson et al, 2004). GM2 synthase deficiency results in hereditary spastic paraplegias and axonal Charcot–Marie–Tooth syndrome (Boukhris et al, 2013; Hong et al, 2021; Lee et al, 2016; Simpson et al, 2004). Neurodegenerative diseases and mental health disorders are also associated with altered ganglioside expression (Itokazu et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis

Fuchigami,

Itokazu,

2023

Glia

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The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia‐like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogeneous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent on their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3‐synthase knockout (GD3S‐KO) mouse brains. The specific roles of GD3 in determining the stage and cell‐lineage determination of NSCs remain unclear, since global GD3S‐KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here, we show that inducible GD3 deletion in postnatal radial glia‐like NSCs promotes NSC activation, resulting in the loss of the long‐term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S‐conditional‐knockout mice led to the impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia‐like NSCs in the adult NSC niche.

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“…For example, loss of GM3 synthase leads to human autosomal recessive infantile-onset symptomatic epilepsy syndrome and Rett syndrome like disorder (Lee et al, 2016; Simpson et al, 2004). GM2 synthase deficiency results in hereditary spastic paralegias and axonal Charcot-Marie-Tooth syndrome (Boukhris et al, 2013; Hong et al, 2021; Lee et al, 2016; Simpson et al, 2004). Neurodegenerative diseases and mental health disorders are also associated with altered ganglioside expression (Itokazu et al, 2023).…”

Section: Introductionmentioning

confidence: 99%

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis

Fuchigami

Itokazu

2023

Preprint

View full text Add to dashboard Cite

The postnatal neural stem cell (NSC) pool hosts quiescent and activated radial glia-like NSCs contributing to neurogenesis throughout adulthood. However, the underlying regulatory mechanism during the transition from quiescent NSCs to activated NSCs in the postnatal NSC niche is not fully understood. Lipid metabolism and lipid composition play important roles in regulating NSC fate determination. Biological lipid membranes define the individual cellular shape and help maintain cellular organization and are highly heterogenous in structure and there exist diverse microdomains (also known as lipid rafts), which are enriched with sugar molecules, such as glycosphingolipids. An often overlooked but key aspect is that the functional activities of proteins and genes are highly dependent upon their molecular environments. We previously reported that ganglioside GD3 is the predominant species in NSCs and that the reduced postnatal NSC pools are observed in global GD3-synthase knockout (GD3S-KO) mouse brains. The specific roles of GD3 in determining the stage and cell-lineage determination of NSCs remain unclear, since global GD3S-KO mice cannot distinguish if GD3 regulates postnatal neurogenesis or developmental impacts. Here we show that inducible GD3 deletion in postnatal radial glia-like NSCs promotes the NSC activation, resulting in the loss of the long-term maintenance of the adult NSC pools. The reduced neurogenesis in the subventricular zone (SVZ) and the dentate gyrus (DG) of GD3S-conditional-knockout mice led to impaired olfactory and memory functions. Thus, our results provide convincing evidence that postnatal GD3 maintains the quiescent state of radial glia-like NSCs in the adult NSC niche.

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A Compound Heterozygous Pathogenic Variant in B4GALNT1 Is Associated With Axonal Charcot-Marie-Tooth Disease

Cited by 8 publications

References 48 publications

Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis

Machine Learning-Based Identification of B4GALNT1 as a Key Player in Hepatocellular Carcinoma: A Comprehensive Bioinformatics and Structural Analysis

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis

Ganglioside GD3 regulates neural stem cell quiescence and controls postnatal neurogenesis

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