一种TBCB的创始变异与全球发育延迟,自闭症谱和性表现有关
Sharon Bratman Morag1, Chen Itzkovich2, Alina Kurolap3
1Internal Medicine B, Rambam Health Care Campus, Israel; Genetic Institute, Rambam Health Care Campus, Israel.
概括
一种新型的TBCB基因变异导致一种罕见的遗传性性形 (HSP) 与发育迟缓和自闭症. 这一发现突显了TBCB在人类中枢神经系统发育和轴突功能中的关键作用.
科学领域:
- 遗传学和分子生物学
- 神经科学
- 发育生物学
背景情况:
- 遗传性性 (HSP) 包括各种由轴突退化的孟德尔性疾病.
- 微管功能障碍是HSP中轴突动力学受损的一个已知因素.
- 编码图布林折叠协因子B的TBCB对α-异构体动力学和神经元轴突生长至关重要.
研究的目的:
- 确定一种新的复杂遗传性性 (HSP) 的遗传原因.
- 描述新发现的TBCB变异的功能后果.
- 研究TBCB在人类中枢神经系统 (CNS) 发育中的作用.
主要方法:
- 在受影响的个体中,外体测序发现了同胞性TBCB变体 (c.589T>A p.
- 功能性研究使用了酵母 (Saccharomyces cerevisiae) 和果 (Drosophila melanogaster) 的模型.
- 在患者衍生的纤维细胞中分析了TBCB表达和局部化.
主要成果:
- 受影响的个体出现了童年晚期发作的性,全身发育迟缓和自闭症谱系障碍.
- 在受影响个体的纤维细胞中观察到降低的TBCB蛋白水平.
- 携带同源的TBCB突变的酵母和Drosophila模型表现出功能丧失的表型,包括对贝诺米尔的敏感性增加,生存率降低和爬能力受损.
结论:
- 描述了一种与TBCB创始变体相关的新型神经发育障碍.
- 这种变异导致TBCB蛋白功能显著降低.
- 在人类中枢神经系统的发育和轴突功能中,TBCB起着至关重要的作用.
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