A novel family illustrating the mild phenotypic spectrum of TUBB2B variants

Dekker, Jordy; Diderich, Karin E. M.; Schot, Rachel; Husen, S.; Dremmen, Marjolein H G; Go, Attie T.J.I.; Weerts, Marjolein J.A.; Slegtenhorst, Marjon A. van; Mancini, Grazia M.S.

doi:10.1016/j.ejpn.2021.09.007

Cited by 6 publications

(4 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Other than 6TI, repeated PPIs of γ -tubulin subtypes (TUBGCP2, TUBGCP3, TUBGCP4, and TUBGCP5) were observed, and such involvement of γ -tubulins subtypes was previously reported to play essential role in GCP formation during assembly of microtubules. GCP abnormalities were earlier reported in cancer progression, retinopathy, and neuronal abnormalities [ 23 , 33 , 34 ]. Similarly, other additional tubulin isotypes TUBB2B, TUBB8, and TUBA1C, which I observed in first level of our selection steps, were previously reported to involve in nucleation of MT, cancer progression, oocyte maturation, and neuronal abnormalities [ 23 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 92%

“…GCP abnormalities were earlier reported in cancer progression, retinopathy, and neuronal abnormalities [ 23 , 33 , 34 ]. Similarly, other additional tubulin isotypes TUBB2B, TUBB8, and TUBA1C, which I observed in first level of our selection steps, were previously reported to involve in nucleation of MT, cancer progression, oocyte maturation, and neuronal abnormalities [ 23 , 35 , 36 ].…”

Section: Discussionmentioning

confidence: 92%

“…Increasing number of regulatory proteins and subpopulation of tubulin proteins are being reported with poor understanding in their association with microtubule assembly and disassembly. In different cell types, tubulin isotypes are expressed at different levels with various cellular functions by multiple genes [ 1 , 2 , 7 , 23 ]. In this paper, the selection of 6TI was based on the manual curation, giving importance to all three tubulin classes ( α -, β -, & γ -tubulins).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Prediction of anti-microtubular target proteins of tubulins and their interacting proteins using Gene Ontology tools

Babu

2023

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

Background Tubulins are highly conserved globular proteins involved in stabilization of cellular cytoskeletal microtubules during cell cycle. Different isoforms of tubulins are differentially expressed in various cell types, and their protein–protein interactions (PPIs) analysis will help in identifying the anti-microtubular drug targets for cancer and neurological disorders. Numerous web-based PPIs analysis methods are recently being used, and in this paper, I used Gene Ontology (GO) tools, e.g., Stringbase, ProteomeHD, GeneMANIA, and ShinyGO, to identify anti-microtubular target proteins by selecting strongly interacting proteins of tubulins. Results I used 6 different human tubulin isoforms (two from each of α-, β-, and γ-tubulin) and found several thousands of node-to-node protein interactions (highest 4956 in GeneMANIA) and selected top 10 strongly interacting node-to-node interactions with highest score, which included 7 tubulin family protein and 6 non-tubulin family proteins (total 13). Functional enrichment analysis indicated a significant role of these 13 proteins in nucleation, polymerization or depolymerization of microtubules, membrane tethering and docking, dorsal root ganglion development, mitotic cycle, and cytoskeletal organization. I found γ-tubulins (TUBG1, TUBGCP4, and TUBBGCP6) were known to contribute majorly for tubulin-associated functions followed by α-tubulin (TUBA1A) and β-tubulins (TUBB AND TUBB3). In PPI results, I found several non-tubular proteins interacting with tubulins, and six of them (HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41) were found closely associated with their functions. Conclusions Increasing number of regulatory proteins and subpopulation of tubulin proteins are being reported with poor understanding in their association with microtubule assembly and disassembly. The functional enrichment analysis of tubulin isoforms using recent GO tools resulted in identification of γ-tubulins playing a key role in microtubule functions and observed non-tubulin family of proteins HTT, DPYSL2, SKI, UNC5C, NINL, and DDX41 strongly interacting functional proteins of tubulins. The present study yields a promising model system using GO tools to narrow down tubulin-associated proteins as a drug target in cancer, Alzheimer’s, neurological disorders, etc.

show abstract

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Prediction of anti-microtubular target proteins of tubulins and their interacting proteins using Gene Ontology tools

Babu

2023

Journal of Genetic Engineering and Biotechnology

View full text Add to dashboard Cite

show abstract

“…The top PCE-associated gene found to display differential methylation at 0 y was TUBB2B. This gene is associated with malformations of cortical development 55 , and mutations in TUBB2B are associated with developmental delays 56 . The top CpG site displaying differential methylation at 7 y was in the gene LZTS2.…”

Section: Prenatal Cannabis Exposure and Differential Dna Methylation ...mentioning

confidence: 99%

Prenatal cannabis exposure alters offspring DNA methylation at genes involved in neurodevelopment, across the life course

Osborne

Noble

Adams

et al. 2023

Preprint

View full text Add to dashboard Cite

Prenatal cannabis exposure (PCE) is of increasing concern globally, due to the potential impact on offspring neurodevelopment, and its association with childhood and adolescent brain development and cognitive function. However, a lack of research addressing the molecular impact of PCE means that it is not known whether PCE can be considered causative for adverse child neurodevelopment, or whether it is simply correlational. To address this knowledge gap, here we present epigenome-wide association study data across multiple timepoints, examining the effect of PCE and co-exposure with tobacco using two longitudinal studies, the Avon Longitudinal Study of Parents and Children (ALSPAC) and the Christchurch Health and Development Study (CHDS) at birth (0 y), 7 y and 15-17 y (ALSPAC), and ~27 y (CHDS). Our findings reveal genome-wide significant DNA methylation differences in offspring at 0 y, 7 y, 15-17 y and 27 y associated with PCE alone, and co-exposure with tobacco. Importantly, we identified significantly differentially methylated CpG sites within the genes LZTS2, NPSR1, NT5E, CRP2, DOCK8, COQ5 and LPAR5 that are shared between different time points throughout development in offspring. Notably, functional pathway analysis showed enrichment for differential DNA methylation in neurodevelopmental and schizophrenia pathways, and this was consistent across all timepoints in both cohorts. Given the increasing volume of epidemiological evidence that suggests a link between PCE and adverse neurodevelopmental outcomes in exposed offspring, this work highlights the need for further investigation into PCE, particularly in larger cohorts.

show abstract

Developmental and behavioral phenotypic outcomes associated with Tubulinopathy conditions

Fidler,

Van Deusen,

Cushion

2024

International Review of Research in Developmental Disabilities

View full text Add to dashboard Cite

A novel family illustrating the mild phenotypic spectrum of TUBB2B variants

Cited by 6 publications

References 37 publications

Prediction of anti-microtubular target proteins of tubulins and their interacting proteins using Gene Ontology tools

Prediction of anti-microtubular target proteins of tubulins and their interacting proteins using Gene Ontology tools

Prenatal cannabis exposure alters offspring DNA methylation at genes involved in neurodevelopment, across the life course

Developmental and behavioral phenotypic outcomes associated with Tubulinopathy conditions

Contact Info

Product

Resources

About