%0 Case Reports
%T A New Phenotype of TUBB4A Mutation in a Family With Adult-Onset Progressive Spastic Paraplegia and Isolated Hypomyelination Leukodystrophy: A Case Report and Literature Review.
%A Hsieh PC
%A Yu PS
%A Fan WL
%A Wang CC
%A Chao CY
%A Wu YR
%J J Mov Disord
%V 17
%N 1
%D 2024 Jan 23
%M 37867417
%F 4.229
%R 10.14802/jmd.23142
%X Tubulin beta 4A class IVa (TUBB4A) spectrum disorders include 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) on 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 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 or extrapyramidal symptoms. In the literature, HSP is considered a TUBB4A spectrum disorder.