Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome

Muthusamy, Babylakshmi; Nguyen, Thong Tien; Bandari, Aravind K.; Basheer, Salah; Selvan, Lakshmi Dhevi N.; Chandel, Deepshikha; Manoj, J. Mammen; Gayen, Srimonta; Seshagiri, Somasekar; Girimaji, Satish Chandra; Pandey, Akhilesh

doi:10.1016/j.ejmg.2019.02.007

Cited by 14 publications

(10 citation statements)

References 41 publications

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“…Interestingly, this individual has the same mutation, R110W, that was identified in several individuals with craniosynostosis and nonsyndromic ID (Table 2) [86][87][88]. Finally, a splicing mutation that deletes two amino acids from HUWE1 was found in a family that potentially has Say-Meyer syndrome, another syndromic form of ID (Table 2) [90]. Taken as a whole, these studies suggest that mutations in HUWE1 potentially result in several types of syndromic ID, including a potential causal link to JMB.…”

Section: Huwe1 Mutations In Syndromic and Nonsyndromic Intellectual Dmentioning

confidence: 67%

Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease

Giles

Grill

2020

Neural Dev

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Huwe1 is a highly conserved member of the HECT E3 ubiquitin ligase family. Here, we explore the growing importance of Huwe1 in nervous system development, function and disease. We discuss extensive progress made in deciphering how Huwe1 regulates neural progenitor proliferation and differentiation, cell migration, and axon development. We highlight recent evidence indicating that Huwe1 regulates inhibitory neurotransmission. In covering these topics, we focus on findings made using both vertebrate and invertebrate in vivo model systems. Finally, we discuss extensive human genetic studies that strongly implicate HUWE1 in intellectual disability, and heighten the importance of continuing to unravel how Huwe1 affects the nervous system.

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Section: Huwe1 Mutations In Syndromic and Nonsyndromic Intellectual Dmentioning

confidence: 67%

Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease

Giles

Grill

2020

Neural Dev

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“…The punctate distribution of HUWE1 throughout the cytosol may also demarcate protein QC hubs in which misfolded proteins have been hypothesised to accumulate in. Mutations in HUWE1 have also been implicated in intellectual disabilities, highlighting its potential importance in proper neuronal development [ 8–11 ].…”

Section: Protein Complexesmentioning

confidence: 99%

It's not just a phase; ubiquitination in cytosolic protein quality control

Baker

Bernardini

2021

Biochemical Society Transactions

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The accumulation of misfolded proteins is associated with numerous degenerative conditions, cancers and genetic diseases. These pathological imbalances in protein homeostasis (termed proteostasis), result from the improper triage and disposal of damaged and defective proteins from the cell. The ubiquitin-proteasome system is a key pathway for the molecular control of misfolded cytosolic proteins, co-opting a cascade of ubiquitin ligases to direct terminally damaged proteins to the proteasome via modification with chains of the small protein, ubiquitin. Despite the evidence for ubiquitination in this critical pathway, the precise complement of ubiquitin ligases and deubiquitinases that modulate this process remains under investigation. Whilst chaperones act as the first line of defence against protein misfolding, the ubiquitination machinery has a pivotal role in targeting terminally defunct cytosolic proteins for destruction. Recent work points to a complex assemblage of chaperones, ubiquitination machinery and subcellular quarantine as components of the cellular arsenal against proteinopathies. In this review, we examine the contribution of these pathways and cellular compartments to the maintenance of the cytosolic proteome. Here we will particularly focus on the ubiquitin code and the critical enzymes which regulate misfolded proteins in the cytosol, the molecular point of origin for many neurodegenerative and genetic diseases.

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“…Another example was Huwe1 , which encodes an E3 ubiquitin ligase, and plays a key role in cerebral cortex neurogenesis ( Zhao et al, 2009 ; D’Arca et al, 2010 ). Mutations in this gene were reported in including both non-syndromic and syndromic forms of X-linked intellectual disability ( Moortgat et al, 2018 ; Muthusamy et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-Wide Identification of G-to-A RNA Editing in Chronic Social Defeat Stress Mouse Models

Ren

Wei

et al. 2021

Front. Genet.

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Emerging evidence suggests that RNA editing is associated with stress, neurological diseases, and psychiatric disorders. However, the role of G-to-A RNA editing in chronic social defeat stress (CSDS) remains unclear. We herein identified G-to-A RNA editing and its changes in the ventral tegmental area (VTA), a key region of the brain reward system, in CSDS mouse models under emotional stress (ES) and physiological stress (PS) conditions. Our results revealed 3812 high-confidence G-to-A editing events. Among them, 56 events were significantly downregulated while 23 significantly upregulated in CSDS compared to controls. Moreover, divergent editing patterns were observed between CSDS mice under ES and PS conditions, with 42 and 21 events significantly upregulated in PS and ES, respectively. Interestingly, differential RNA editing was enriched in genes with multiple editing events. Genes differentially edited in CSDS included those genetically associated with mental or neurodevelopmental disorders, especially mood disorders, such as FAT atypical cadherin 1 and solute carrier family 6 member 1. Notably, changes of G-to-A RNA editing were also implicated in ionotropic glutamate receptors, a group of well-known targets of adenosine-to-inosine RNA editing. Such results demonstrate dynamic G-to-A RNA editing changes in the brain of CSDS mouse models, underlining its role as a potential molecular mechanism of CSDS and stress-related diseases.

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Exome sequencing reveals a novel splice site variant in HUWE1 gene in patients with suspected Say-Meyer syndrome

Cited by 14 publications

References 41 publications

Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease

Roles of the HUWE1 ubiquitin ligase in nervous system development, function and disease

It's not just a phase; ubiquitination in cytosolic protein quality control

Transcriptome-Wide Identification of G-to-A RNA Editing in Chronic Social Defeat Stress Mouse Models

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