Novel Compound Heterozygous Variants in <i>TBCD</i> Gene Associated with Infantile Neurodegenerative Encephalopathy
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 disord...
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| Main Authors: | , , , , , |
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| Format: | Book |
| Published: |
MDPI AG,
2021-12-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | 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 <i>TBCD</i> 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 <i>TBCD</i> pathogenic variants and provided insight into the protein structural alteration that may contribute to this chaperone-associated tubulinopathy. |
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| Item Description: | 10.3390/children8121140 2227-9067 |