ArticleHuman molecular genetics2016
Infantile neurodegenerative disorder associated with mutations in TBCD, an essential gene in the tubulin heterodimer assembly pathway.
Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- ThermoTargetMiner as a proteome integral solubility alteration target database for prospective drugs against lung cancer.Communications chemistry · 2026Article
- Movement Disorders in Developmental and Epileptic Encephalopathies.Movement disorders clinical practice · 2026Review
- Association Between Maternal Gestational Diabetes, Cord Blood DNA Methylation, and Offspring Neurodevelopment.International journal of molecular sciences · 2026Article
- Cryo-ET suggests tubulin chaperones form a subset of microtubule lumenal particles with a role in maintaining neuronal microtubules.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- CRISPR/Cas9 andInternational journal of molecular sciences · 2023Article
- Clinical and genetic characterization of a Taiwanese cohort with spastic paraparesis combined with cerebellar involvement.Frontiers in neurology · 2022Article
- Novel Compound Heterozygous Variants inChildren (Basel, Switzerland) · 2021Article
- Epstein-Barr virus-based plasmid enables inheritable transgene expression in mouse cerebral cortex.PloS one · 2021Article
- The utility of whole exome sequencing for identification of the molecular etiology in autosomal recessive developmental and epileptic encephalopathies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Article
- DNA methylation changes in infants between 6 and 52 weeks.Scientific reports · 2019Article
- Biallelic pathogenic variants in TBCD-related neurodevelopment disease with mild clinical features.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Article
- Single-cell RNA-seq variant analysis for exploration of genetic heterogeneity in cancer.Scientific reports · 2019Article
- A Faroese founder variant in TBCD causes early onset, progressive encephalopathy with a homogenous clinical course.European journal of human genetics : EJHG · 2018Article
- Cortical atrophy and hypofibrinogenemia due to FGG and TBCD mutations in a single family: a case report.BMC medical genetics · 2018Article
- Nucleotide Binding to ARL2 in the TBCD∙ARL2∙β-Tubulin Complex Drives Conformational Changes in β-Tubulin.Journal of molecular biology · 2017Article
- PRUNE is crucial for normal brain development and mutated in microcephaly with neurodevelopmental impairment.Brain : a journal of neurology · 2017Article
- TBCD may be a causal gene in progressive neurodegenerative encephalopathy with atypical infantile spinal muscular atrophy.Journal of human genetics · 2017Article
- A Trimer Consisting of the Tubulin-specific Chaperone D (TBCD), Regulatory GTPase ARL2, and β-Tubulin Is Required for Maintaining the Microtubule Network.The Journal of biological chemistry · 2017Article
- Update on the Genetics of Dystonia.Current neurology and neuroscience reports · 2017Review
- Tubulin Folding Cofactor D Deficiency: Missing the Diagnosis With Whole Exome Sequencing.Child neurology openArticle
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
Abstract
Mutation in a growing spectrum of genes is known to either cause or contribute to primary or secondary microcephaly. In primary microcephaly the genetic determinants frequently involve mutations that contribute to or modulate the microtubule cytoskeleton by causing perturbations of neuronal proliferation and migration. Here we describe four patients from two unrelated families each with an infantile neurodegenerative disorder characterized by loss of developmental milestones at 9–24 months of age followed by seizures, dystonia and acquired microcephaly. The patients harboured homozygous missense mutations (A475T and A586V) in TBCD, a gene encoding one of five tubulin-specific chaperones (termed TBCA-E) that function in concert as a nanomachine required for the de novo assembly of the α/β tubulin heterodimer. The latter is the subunit from which microtubule polymers are assembled. We found a reduced intracellular abundance of TBCD in patient fibroblasts to about 10% (in the case of A475T) or 40% (in the case of A586V) compared to age-matched wild type controls. Functional analyses of the mutant proteins revealed a partially compromised ability to participate in the heterodimer assembly pathway. We show via in utero shRNA-mediated suppression that a balanced supply of tbcd is critical for cortical cell proliferation and radial migration in the developing mouse brain. We conclude that TBCD is a novel functional contributor to the mammalian cerebral cortex development, and that the pathological mechanism resulting from the mutations we describe is likely to involve compromised interactions with one or more TBCD-interacting effectors that influence the dynamics and behaviour of the neuronal cytoskeleton.
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