A novel TUBB3 mutation in a sporadic patient with asymmetric cortical dysplasia
A novel TUBB3 mutation in a sporadic patient with asymmetric cortical dysplasia
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散发性不对称皮质发育不良患者中的新型 TUBB3 突变
DOI：
10.1002/ajmg.a.37545
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发表时间：
2015
期刊：
影响因子：
2
通讯作者：
Yamamoto T.
中科院分区：
文献类型：
--
作者：
Shimojima K;Okamoto N;Yamamoto T.
分子技术的最新进展导致了几个与人类皮质发育畸形(MCDs)相关的基因的发现。β-微管蛋白III类基因(TUBB3)被鉴定为MCDs的致病基因。尽管老鼠模型实验没有发现任何神经元迁移障碍的结果，但已经在先天性眼外肌纤维化患者中发现了人类TUBB3突变。自从发现TUBB3突变以来，只发现了15个突变。在这项研究中，通过下一代测序进行全面的突变筛查，在一名与轻度MCD相关的中度发育迟缓的散发性患者中发现了一个新的TUBB3突变(p.Ser230Leu)。与携带α-微管蛋白1a类基因(TUBA1A)突变的患者相比，携带TUBB3突变的患者具有较轻的表型表现和较轻的MCD。因此，有轻微MCD表现的患者可能被低估，TUBB3突变可能很少被发现。应该积累更多的基因型-表型信息，以进一步了解TUBB3的功能相关性。©2016 Wiley期刊，Inc.
Recent advances in molecular technology have led to the discovery of several genes related to human malformations of cortical development (MCDs). The beta‐tubulin class III gene (TUBB3) was identified as a gene responsible for MCDs. Although mouse‐model experiments have not revealed any findings of neuronal migration disorders, humanTUBB3mutations have been identified in patients with congenital fibrosis of the extraocular muscles. Since the discovery of aTUBB3mutation, only 15 mutations have been identified. In this study, comprehensive mutation screening through next‐generation sequencing identified a novelTUBB3mutation (p.Ser230Leu) in a sporadic patient with moderate developmental delay associated with mild MCD. Compared to patients with the alpha‐tubulin class 1a gene (TUBA1A) mutations, patients withTUBB3mutations show milder phenotypic manifestations and milder MCD. Therefore, patients with milder MCD manifestations may be under‐diagnosed, andTUBB3mutations may be rarely identified. Additional genotype–phenotype information should be accumulated for further understanding of theTUBB3functional relevance. © 2016 Wiley Periodicals, Inc.