Abstract

Tubulin Beta 4A Class IVa (TUBB4A) spectrum disorders have been reported as autosomal dominant dystonia type 4 or hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC syndrome). However, in rare cases, only mild hypomyelination in the cortex with no basal ganglia atrophy may be observed. We report a case of a family with TUBB4A mutation and complicated hereditary spasticity paraplegia (HSP). We performed quadro whole exome sequencing (WES) for the family to identify the causative gene of progressive spastic paraparesis with isolated hypomyelination leukodystrophy. We identified a novel TUBB4A p.F341L mutation, which was present in all three affected patients but was absent in the unaffected father. The affected patients presented with adult onset TUBB4A disorder, predominant spastic paraparesis with/without ataxia, and brain hypomyelination with no cognitive impairment and extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.

• Keywords: TUBB4A, hereditary spasticity paraplegia (HSP), whole exome sequencing (WES);