Novel Compound Heterozygous Variants in TBCD Gene Associated with Infantile Neurodegenerative Encephalopathy

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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.

National Taiwan University Hospital

06-25-2019

Children Basel

Affiliations

¹Department of Medical Genetics, National Taiwan University Hospital, Taipei 100226, Taiwan.
²Department of Obstetrics and Gynecology, National Taiwan University Hospital, Taipei 100226, Taiwan.
³Department of Pediatrics, National Taiwan University Hospital, Taipei 100226, Taiwan.
⁴Department of Pediatrics, Changhua Christian Hospital, Changhua 50006, Taiwan.
⁵Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu 300093, Taiwan.