Department of Precision Medicine, University of Campania, Luigi Vanvitelli, Caserta, Italy.
Telethon Institute of Genetics and Medicine, Pozzuoli, Italy.
J Neurol. 2023 Oct;270(10):5057-5063. doi: 10.1007/s00415-023-11816-w. Epub 2023 Jul 7.
Tubulinopathies encompass neurodevelopmental disorders caused by mutations in genes encoding for different isotypes of α- and β-tubulins, the structural components of microtubules. Less frequently, mutations in tubulins may underlie neurodegenerative disorders. In the present study, we report two families, one with 11 affected individuals and the other with a single patient, carrying a novel, likely pathogenic, variant (p. Glu415Lys) in the TUBA4A gene (NM_006000). The phenotype, not previously described, is that of spastic ataxia. Our findings widen the phenotypic and genetic manifestations of TUBA4A variants and add a new type of spastic ataxia to be taken into consideration in the differential diagnosis.
微管病涵盖了由不同微管蛋白 α-和 β-异构体编码基因的突变引起的神经发育障碍，微管蛋白是微管的结构组成部分。较少见的是，微管蛋白的突变可能导致神经退行性疾病。在本研究中，我们报告了两个家系，一个家系有 11 名受影响的个体，另一个家系仅有一名患者，携带 TUBA4A 基因（NM_006000）中一种新的、可能致病的变异（p. Glu415Lys）。该表型以前并未描述过，表现为痉挛性共济失调。我们的发现拓宽了 TUBA4A 变异的表型和遗传表现，并为鉴别诊断增加了一种新的痉挛性共济失调类型。
