112 Axonal polyneuropathy with onset in young adulthood due to TUBB3 mutation

Abstract

IntroductionThe TUBB3 gene encodes the protein Beta-tubulin isotype III, a component of the microtubule cytoskeleton. Mutations in this gene have been associated with axonal polyneuropathy, however usually associated with congenital fibrosis of the extraocular muscles (CFOEM) and other abnormalities of cerebral development.1 2 We report a case of isolated neuropathy associated with a TUBB3 mutation.MethodsCase report - clinical information and next generation sequencing results were obtained.ResultsA 64 year old man presented with a severe, progressive, length dependent sensorimotor polyneuropathy which commenced in his late twenties. There was no clinical involvement of the extraocular muscles and cognition was normal. Family history was limited, but there were no other members affected.The patient had previously been extensively investigated including sural nerve biopsy, which confirmed axonal neuropathy without a specific diagnosis. Intravenous immunoglobulins and steroids had been trialled without benefit.A neuromuscular gene panel utilising next generation sequencing was performed and demonstrated heterozygosity for a variant of the TUBB3 gene (D417N substitution).Case series describing TUBB3 mutations show a large heterogeneity in phenotypic expression depending on the amino acid substitution.2–4 There is also heterogeneity in patients with D417N mutations, although a small number have been reported to develop a polyneuropathy without CFOEM1.ConclusionsThis case strengthens previous reports that TUBB3 mutation can be associated with a pure, axonal, sensorimotor polyneuropathy and highlights the use of next generation sequencing in streamlining the diagnostic process.ReferenceTischfield M, et al. Human TUBB3 mutations perturb microtubule dynamics, kinesin interactions, and axon guidance. Cell 2010;140(1):pp.74–87.Ncbi.nlm.nih.gov. (2019). Congenital fibrosis of the extraocular muscles - Conditions - GTR - NCBI. [online] Available at: https://www.ncbi.nlm.nih.gov/gtr/conditions/CN043677/ [Accessed 14 Feb. 2019].Omim.org. (2019). OMIM Entry - * 602661 - TUBULIN, BETA-3; TUBB3. [online] Available at: https://www.omim.org/entry/602661 [Accessed 14 Feb. 2019].Krupa, K. and Bekiesinska-Figatowska, M. (2013). Congenital and Acquired Abnormalities of the Corpus Callosum: A Pictorial Essay. BioMed Research International, 2013, pp.1–14.