Loss-of-Function Plays a Major Role in Early Neurogenesis of Tubulin α-1 A (TUBA1A) Mutation-Related Brain Malformations

Xie, Liling; Huang, Ju; Dai, Lei; Luo, Jiefeng; Zhang, Jiejie; Peng, Qiaozhen; Sun, Jingchi; Zhang, Weishe

doi:10.1007/s12035-020-02193-w

Cited by 6 publications

(6 citation statements)

References 42 publications

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“…Subsequently, four representative genes ( Stmn2 , Tuba1a , Gpm6a and Tagln3 ) specifically expressed in the neurons were selected (Figure 4C ). Stmn2 , Tuba1a and Gpm6a have been confirmed to play crucial roles in early neurogenesis ( 20 , 21 ) and the maintenance of neuronal morphology ( 22 , 23 ).…”

Section: Resultsmentioning

confidence: 99%

EmAtlas: a comprehensive atlas for exploring spatiotemporal activation in mammalian embryogenesis

Zheng

Liang

Long

et al. 2022

Nucleic Acids Research

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The emerging importance of embryonic development research rapidly increases the volume for a professional resource related to multi-omics data. However, the lack of global embryogenesis repository and systematic analysis tools limits the preceding in stem cell research, human congenital diseases and assisted reproduction. Here, we developed the EmAtlas, which collects the most comprehensive multi-omics data and provides multi-scale tools to explore spatiotemporal activation during mammalian embryogenesis. EmAtlas contains data on multiple types of gene expression, chromatin accessibility, DNA methylation, nucleosome occupancy, histone modifications, and transcription factors, which displays the complete spatiotemporal landscape in mouse and human across several time points, involving gametogenesis, preimplantation, even fetus and neonate, and each tissue involves various cell types. To characterize signatures involved in the tissue, cell, genome, gene and protein levels during mammalian embryogenesis, analysis tools on these five scales were developed. Additionally, we proposed EmRanger to deliver extensive development-related biological background annotations. Users can utilize these tools to analyze, browse, visualize, and download data owing to the user-friendly interface. EmAtlas is freely accessible at http://bioinfor.imu.edu.cn/ematlas.

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Section: Resultsmentioning

confidence: 99%

EmAtlas: a comprehensive atlas for exploring spatiotemporal activation in mammalian embryogenesis

Zheng

Liang

Long

et al. 2022

Nucleic Acids Research

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“…A large majority of TUBA1A missense variants might be deleterious according to Hebebrand et al (2019). One of the possible mechanisms by which the pathogenic mutations in the tubulin genes result in the characteristic brain abnormalities is diminishing the heterodimer formation and incorporation into microtubules (Tischfield & Engle, 2010; Xie et al, 2020). However, the mechanism of all mutations is still not well understood.…”

Section: Discussionmentioning

confidence: 99%

“…In the second case, due to the early term of the gestation, the spinal cord was hence not available for evaluation. Hitherto, the most severe TUBA1A histological phenotype was the association of lissencephaly with corpus callosum agenesis, brainstem, and vermian hypoplasia; and in one case, with hydrocephaly (Bahi‐Buisson et al, 2014; Xie et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…In existing literature, both TUBA1A and TUBB2B mutations are commonly associated with a number of complex cortical malformations and cytoarchitectural disorders, brainstem, and cerebellar hypoplasia/dysplasia and seldomly, unusual "open-lip" schizencephaly (Aiken et al, 2019;Bahi-Buisson et al, 2014;Bahi-Buisson & Cavallin, 1993;Gardner et al, 2018;Hebebrand et al, 2019;R. A. Kumar et al, 2010;Romaniello et al, 2018;Xie et al, 2020). So far, the involvement of the spinal cord has been documented in only one case in association with TUBB2B p.Cys239Phe mutation (Laquerriere et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Broadening the phenotypic spectrum of TUBA1A tubulinopathy to syndromic arthrogryposis multiplex congenita

Weber

Jaber

Encha‐Razavi

et al. 2022

American J of Med Genetics Pt A

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The recent finding that some patients with fetal akinesia deformation sequence (FADS) carry variants in the TUBB2B gene has prompted us to add to the existing literature a first description of two fetal FADS cases carrying TUBA1A variants. Hitherto, only isolated cortical malformations have been described with TUBA1A mutation, including microlissencephaly, lissencephaly, central pachygyria and polymicrogyria‐like cortical dysplasia, generalized polymicrogyria cortical dysplasia, and/or the “simplified” gyral pattern. The neuropathology of our fetal cases shows several common features of tubulinopathies, in particular, the dysmorphism of the basal ganglia, as the most pathognomonic sign. The cortical ribbon anomalies were extremely severe and concordant with the complex cortical malformation. In conclusion, we broaden the phenotypic spectrum of TUBA1A variants, to include FADS.

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“…These include lissencephaly, cerebellar hypoplasia, corpus callosum hypoplasia, and brainstem abnormalities ( 13 , 14 ). This gene is often associated with dyskinesia, epilepsy, cognitive deficits, and other abnormalities ( 15 , 16 ). To date, 77 missense variants have been reported, with most cases exhibiting de novo autosomal dominant inheritance ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Lissencephaly caused by a de novo mutation in tubulin TUBA1A: a case report and literature review

Ren,

Kong,

Liu

et al. 2024

Front. Pediatr.

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Tubulin plays an essential role in cortical development, and TUBA1A encodes a major neuronal α-tubulin. Neonatal mutations in TUBA1A are associated with severe brain malformations, and approximately 70% of patients with reported cases of TUBA1A mutations exhibit lissencephaly. We report the case of a 1-year-old boy with the TUBA1A nascent mutation c.1204C >T, p.Arg402Cys, resulting in lissencephaly, developmental delay, and seizures, with a brain MRI showing normal cortical formation in the bilateral frontal lobes, smooth temporo-parieto-occipital gyri and shallow sulcus. This case has not been described in any previous report; thus, the present case provides new insights into the broad disease phenotype and diagnosis associated with TUBA1A mutations. In addition, we have summarized the gene mutation sites, neuroradiological findings, and clinical details of cases previously described in the literature and discussed the differences that exist between individual cases of TUBA1A mutations through a longitudinal comparative analysis of similar cases. The complexity of the disease is revealed, and the importance of confirming the genetic diagnosis from the beginning of the disease is emphasized, which can effectively shorten the diagnostic delay and help clinicians provide genetic and therapeutic counseling.

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Loss-of-Function Plays a Major Role in Early Neurogenesis of Tubulin α-1 A (TUBA1A) Mutation-Related Brain Malformations

Cited by 6 publications

References 42 publications

EmAtlas: a comprehensive atlas for exploring spatiotemporal activation in mammalian embryogenesis

EmAtlas: a comprehensive atlas for exploring spatiotemporal activation in mammalian embryogenesis

Broadening the phenotypic spectrum of TUBA1A tubulinopathy to syndromic arthrogryposis multiplex congenita

Lissencephaly caused by a de novo mutation in tubulin TUBA1A: a case report and literature review

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