Broadening the spectrum phenotype of TBCE-related neuron neurodegeneration.

Abstract Background Severe loss of TBCE function has been related to two well-known dysmorphic syndromes, while TBCE hypomorphic variants have been linked to neurodegenerative conditions due to perturbed microtubule dynamics and homeostasis, with signs of central and peripheral nervous system involvement. Method We report on an Italian female originating from Southern Italy who presented early-onset regression and neurodegeneration, with neurological features of tetraparesis and signs of peripheral nervous system involvement. Her brain MRI revealed white matter involvement. Results Analyzing all known hypomyelination leukodystrophies related genes, two mutations in TBCE (NM_001079515) were detected: the missense variant c.464 T > A; p. (Ile155Asn) and the frameshift variant c.924del; p. (Leu309Ter), in compound heterozygosity, already reported in the literature in patients coming from the same geographical area. The clinical phenotype of the proposita was more severe and with an earlier onset than the majority of the patients reported so far. Conclusions Next Generation Sequencing is becoming increasingly necessary to assess unusual phenotypes, with the opportunity to establish prognosis and disease mechanisms, and facilitating differential diagnosis.