Paternal De Novo Variant of TAOK1 in a Fetus With Structural Brain Abnormalities

Yu, Lihua; Yang, Chaoxiang; Shang, Ning; Ding, Hu; Zhu, Juan; Zhu, Yuanyuan; Tan, Haowen; Zhang, Yan

doi:10.3389/fgene.2022.836853

Cited by 4 publications

(3 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A recent report of a de novo frameshift variant in a girl with isolated childhood-onset tremor was also excluded, because, based on the available clinical data, she did not properly fit into the definition of NDD [ 22 ]. Prenatal cases were also excluded [ 17 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Yu et al recently reported one case of brain MRI abnormalities in a fetus with a de novo missense TAOK1 variant, in which bilateral polymicrogyria of the lateral fissure area could not be ruled out by the authors [ 18 ]. It would be interesting to know whether a postnatal MRI would confirm a malformation of cortical development.…”

Section: Discussionmentioning

confidence: 99%

“…To date, the reported data on brain magnetic resonance imaging (MRI) findings in TAOK1 -related patients are scarce and non-specific [ 11 , 16 – 18 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders

Cavalli,

Caraffi,

Rizzi

et al. 2024

BMC Med Genomics

View full text Add to dashboard Cite

Background Thousand and one amino-acid kinase 1 (TAOK1) encodes the MAP3K protein kinase TAO1, which has recently been displayed to be essential for neuronal maturation and cortical differentiation during early brain development. Heterozygous variants in TAOK1 have been reported in children with neurodevelopmental disorders, with or without macrocephaly, hypotonia and mild dysmorphic traits. Literature reports lack evidence of neuronal migration disorders in TAOK1 patients, although studies in animal models suggest this possibility. Case presentation We provide a clinical description of a child with a neurodevelopmental disorder due to a novel TAOK1 truncating variant, whose brain magnetic resonance imaging displays periventricular nodular heterotopia. Conclusions To our knowledge, this is the first report of a neuronal migration disorder in a patient with a TAOK1-related neurodevelopmental disorder, thus supporting the hypothesized pathogenic mechanisms of TAOK1 defects.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders

Cavalli,

Caraffi,

Rizzi

et al. 2024

BMC Med Genomics

View full text Add to dashboard Cite

show abstract

Neurodevelopmental disorder–associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase

et al. 2023

View full text Add to dashboard Cite

Mutations in TAOK1 , which encodes a serine-threonine kinase, are associated with both autism spectrum disorder (ASD) and neurodevelopmental delay (NDD). Here, we investigated the molecular function of this evolutionarily conserved kinase and the mechanisms through which TAOK1 mutations may lead to neuropathology. We found that TAOK1 was abundant in neurons in the mammalian brain and remodeled the neuronal plasma membrane through direct association with phosphoinositides. Our characterization of four NDD-associated TAOK1 mutations revealed that these mutants were catalytically inactive and were aberrantly trapped in a membrane-bound state, which induced abnormal membrane protrusions. Expression of these TAOK1 mutants in cultured mouse hippocampal neurons led to abnormal growth of the dendritic arbor. The coiled-coil region carboxyl-terminal to the kinase domain was predicted to fold into a triple helix, and this region directly bound phospholipids and was required for both membrane association and induction of aberrant protrusions. Autophosphorylation of threonine-440 and threonine-443 in the triple-helical region by the kinase domain blocked the plasma membrane association of TAOK1. These findings define TAOK1 as a plasma membrane remodeling kinase and reveal the underlying mechanisms through which TAOK1 dysfunction may lead to neurodevelopmental disorders.

show abstract

Pleiotropic functions of TAO kinases and their dysregulation in neurological disorders

Byeon,

Yadav

2024

Sci. Signal.

View full text Add to dashboard Cite

Thousand and one amino acid kinases (TAOKs) are relatively understudied and functionally pleiotropic protein kinases that have emerged as important regulators of neurodevelopment. Through their conserved amino-terminal catalytic domain, TAOKs mediate phosphorylation at serine/threonine residues in their substrates, but it is their divergent regulatory carboxyl-terminal domains that confer both exquisite functional specification and cellular localization. In this Review, we discuss the physiological roles of TAOKs and the intricate signaling pathways, molecular interactions, and cellular behaviors they modulate—from cell stress responses, division, and motility to tissue homeostasis, immunity, and neurodevelopment. These insights are then integrated into an analysis of the known and potential impacts of disease-associated variants of TAOKs, with a focus on neurodevelopmental disorders, pain and addiction, and neurodegenerative diseases. Translating this foundation into clinical benefits for patients will require greater structural and functional differentiation of the TAOKs afforded by their individually specialized domains.

show abstract

Paternal De Novo Variant of TAOK1 in a Fetus With Structural Brain Abnormalities

Cited by 4 publications

References 30 publications

Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders

Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders

Neurodevelopmental disorder–associated mutations in TAOK1 reveal its function as a plasma membrane remodeling kinase

Pleiotropic functions of TAO kinases and their dysregulation in neurological disorders

Contact Info

Product

Resources

About