Leventer R J, Pilz D T, Matsumoto N, Ledbetter D H, Dobyns W B
Department of Human Genetics and Department of Neurology, University of Chicago, IL 60637, USA.
Mol Med Today. 2000 Jul;6(7):277-84. doi: 10.1016/s1357-4310(00)01730-5.
Magnetic resonance imaging is now used routinely in the evaluation of developmental and neurological disorders and provides exquisite images of the living human brain. Consequently, it is evident that cortical malformations are more common than previously thought. Among the most severe is classical lissencephaly, in which the cortex lacks the complex folding that characterizes the normal human brain. Lissencephaly includes agyria and pachygyria, and merges with subcortical band heterotopia. Current molecular genetic techniques combined with the identification of affected patients have enabled the detection of two of the genes responsible: LIS1 (PAFAH1B1) on chromosome 17 and DCX (doublecortin) on the X chromosome. This review highlights the discovery of these genes and discusses the advances made in understanding the molecular basis of cortical development and improvements in diagnosis and genetic counseling.
磁共振成像目前常用于评估发育和神经疾病，并能提供活体人类大脑的精细图像。因此，很明显皮质畸形比以前认为的更为常见。最严重的一种是典型无脑回畸形，其中皮质缺乏正常人类大脑所特有的复杂折叠。无脑回畸形包括无脑回和巨脑回，并与皮质下带异位症相关。当前的分子遗传学技术与对受影响患者的识别相结合，已能够检测出两个致病基因：位于17号染色体上的LIS1（PAFAH1B1）和位于X染色体上的DCX（双皮质素）。本综述重点介绍了这些基因的发现，并讨论了在理解皮质发育分子基础方面取得的进展以及诊断和遗传咨询方面的改进。
