Vinters H V, Kerfoot C, Catania M, Emelin J K, Roper S N, DeClue J E
Department of Pathology and Laboratory Medicine (Neuropathology), UCLA Medical Center, Los Angeles, CA 90095, USA.
Epilepsy Res. 1998 Sep;32(1-2):12-23. doi: 10.1016/s0920-1211(98)00036-9.
Cortical dysplasia (CD) broadly defines a complex cerebral malformative lesion associated clinically with intractable, pharmacoresistant epilepsy (including infantile spasms), especially in infants and children. In CD, the spectrum of structural brain abnormalities includes (at a minimum) neuronal dyslamination and (in severe cases) neuronal cytomegaly with cytoskeletal alterations and the presence of gemistocyte-like 'balloon cells'. In some CD variants, the neuropathological features are essentially indistinguishable from those of a tuber of tuberous sclerosis (TSC). Two genes associated with the autosomal dominant, multi-system disorder TSC have recently been cloned: TSC2 (on chromosome 16p13.3) encodes the protein tuberin and TSC1 (on 9q34) encodes hamartin. Tuberin has been immunolocalized to neurons and possibly astrocytes in normal brain and CD/TSC tubers, and is widely expressed in normal viscera; loss of heterozygosity and tissue culture studies suggest it functions as a growth suppressor. The TSC1 gene has been cloned within the last year and hamartin as yet has no well-defined cellular function, though its protein product may also function as a growth suppressor. This article focuses on the cellular pathogenesis of CD and TSC brain lesions and how the two may be biologically related. Studies of how TSC1 and TSC2 function in normal and dysplastic cerebral neocortex may provide a paradigm for understanding the neurobiology of other genes that determine epilepsy-associated cerebral malformations (e.g. lissencephaly, double cortex).
皮质发育异常（CD）广义上定义了一种复杂的脑畸形病变，临床上与难治性、药物抵抗性癫痫（包括婴儿痉挛症）相关，尤其在婴幼儿中多见。在CD中，脑结构异常的范围包括（至少）神经元分层紊乱，在严重病例中还包括神经元细胞肿大、细胞骨架改变以及出现类似肥胖细胞的“气球样细胞”。在一些CD变异型中，神经病理学特征与结节性硬化症（TSC）的结节基本无法区分。最近克隆出了与常染色体显性多系统疾病TSC相关的两个基因：TSC2（位于16号染色体p13.3）编码tuberin蛋白，TSC1（位于9号染色体q34）编码hamartin蛋白。在正常脑和CD/TSC结节中，tuberin蛋白已被免疫定位到神经元，可能还有星形胶质细胞，并且在正常内脏中广泛表达；杂合性缺失和组织培养研究表明它具有生长抑制功能。TSC1基因是去年克隆出来的，hamartin蛋白目前还没有明确的细胞功能，不过其蛋白产物可能也具有生长抑制功能。本文重点关注CD和TSC脑病变的细胞发病机制以及两者在生物学上可能存在的关联。对TSC1和TSC2在正常和发育异常的大脑新皮质中如何发挥功能的研究，可能为理解其他决定癫痫相关脑畸形（如无脑回畸形、双皮质畸形）的基因的神经生物学提供范例。
