Related Experiment Video
Updated: Oct 9, 2025
In Vivo Functional Study of Disease-associated Rare Human Variants Using Drosophila
Published on: August 20, 2019
Novel Compound Heterozygous Variants in TBCD Gene Associated with Infantile Neurodegenerative Encephalopathy
Chih-Ling Chen1,2, Chien-Nan Lee1,2, Yin-Hsiu Chien1,3
1Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan.
Abstract:
Mutations in tubulin-specific chaperon D (TBCD), the gene encoding one of the co-chaperons required for the assembly and disassembly of the α/β-tubulin heterodimers, have been reported to cause perturbed microtubule dynamics, resulting in debilitating early-onset progressive neurodegenerative disorder. Here, we identified two novel TBCD variants, c.1340C>T (p.Ala447Val), and c.817+2T>C, presented as compound heterozygotes in two affected siblings born to unaffected carrier parents. Clinical features included early-onset neurodegeneration, failure to thrive, respiratory failure, hypotonia, muscle weakness and atrophy and seizures. We established the genotype-phenotype relationship of these TBCD pathogenic variants and provided insight into the protein structural alteration that may contribute to this chaperone-associated tubulinopathy.
Insights
Two novel mutations in the tubulin-specific chaperone D (TBCD) gene were identified in siblings with early-onset neurodegeneration. These TBCD variants disrupt microtubule dynamics, causing a severe progressive neurodegenerative disorder.
Area of Science:
- Genetics and Molecular Biology
- Neuroscience
- Cell Biology
Background:
- Mutations in tubulin-specific chaperone D (TBCD) are linked to neurodegenerative disorders.
- TBCD is crucial for the assembly and disassembly of α/β-tubulin heterodimers, impacting microtubule dynamics.
Observation:
- Two novel TBCD variants (c.1340C>T and c.817+2T>C) were identified in compound heterozygotes in two affected siblings.
- The siblings presented with early-onset neurodegeneration, failure to thrive, respiratory failure, hypotonia, muscle weakness, atrophy, and seizures.
Findings:
- The identified TBCD variants are pathogenic and segregate with the disease in the affected family.
- These variants likely perturb microtubule dynamics, contributing to the observed neurodegenerative phenotype.
Implications:
- Establishes a genotype-phenotype correlation for these novel TBCD variants.
- Provides insights into the structural alterations in TBCD that lead to chaperone-associated tubulinopathy.
- Highlights the critical role of TBCD in maintaining neuronal integrity and function.
More Related Videos
09:37Navigating MARRVEL, a Web-Based Tool that Integrates Human Genomics and Model Organism Genetics Information
Published on: August 15, 2019
08:22A Novel Strategy Combining Array-CGH, Whole-exome Sequencing and In Utero Electroporation in Rodents to Identify Causative Genes for Brain Malformations
Published on: December 1, 2017
Related Concept Videos
01:11Genetic Lingo
01:35Pedigree Analysis
01:49Probability Laws
01:43Incomplete Dominance
01:43Sex-linked Disorders
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...