Department of Molecular Biology and Genetics, Johns Hopkins Medical School, 725 North Wolfe St., PCTB 804, Baltimore, MD 21205, United States.
Curr Opin Genet Dev. 2011 Jun;21(3):286-94. doi: 10.1016/j.gde.2011.01.003. Epub 2011 Feb 1.
A spectrum of neurological disorders characterized by abnormal neuronal migration, differentiation, and axon guidance and maintenance have recently been attributed to missense and splice-site mutations in the genes that encode α-tubulin and β-tubulin isotypes TUBA1A, TUBA8, TUBB2B, and TUBB3, all of which putatively coassemble into neuronal microtubules. The resulting nervous system malformations can include different types of cortical malformations, defects in commissural fiber tracts, and degeneration of motor and sensory axons. Many clinical phenotypes and brain malformations are shared among the various mutations regardless of structural location and/or isotype, while others segregate with distinct amino acids or functional domains within tubulin. Collectively, these disorders provide novel paradigms for understanding the biological functions of microtubules and their core components in normal health and disease.
最近，一系列以神经元迁移、分化和轴突导向及维持异常为特征的神经紊乱被归因于编码微管蛋白α和β异构型的基因 TUBA1A、TUBA8、TUBB2B 和 TUBB3 中的错义突变和剪接位点突变，这些基因均假定共同组装成神经元微管。由此产生的神经系统畸形可能包括不同类型的皮质畸形、联络纤维束的缺陷以及运动和感觉轴突的退化。各种突变之间存在许多共同的临床表型和脑畸形，无论结构位置和/或异构型如何，而其他突变则与微管和核心成分的不同氨基酸或功能域分离。这些疾病共同为理解微管及其核心成分在正常健康和疾病中的生物学功能提供了新的范例。
