Abstract：
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.
摘要：
据报道，微管蛋白β4AIVa类（TUBB4A）谱系疾病为常染色体显性遗传性肌张力障碍4型或伴有基底神经节和小脑萎缩的脊髓过多症（H-ABC综合征）。然而,在极少数情况下，在皮质中仅观察到轻度的髓鞘减少，没有基底神经节萎缩。我们报告了一例TUBB4A突变和复杂的遗传性痉挛截瘫（HSP）的家庭。我们对该家族进行了四重全外显子组测序（WES），以鉴定患有孤立性骨髓过多性白细胞营养不良的进行性痉挛性轻瘫的致病基因。我们鉴定了一个新的TUBB4Ap.F341L突变，在所有三名受影响的患者中都存在，但在未受影响的父亲中不存在。受影响的患者出现成人发作的TUBB4A障碍，伴有/不伴有共济失调的主要痉挛性轻瘫，和无认知障碍和锥体外系症状的脑髓鞘减少。在文学中,HSP被认为是TUBB4A谱系障碍。
