A search for a mutation associated with narcolepsy.

令人震惊的证据表明，嗜睡症与HLA DR2（DR15）抗原几乎100%相关，这是阐明这种睡眠障碍的分子基础的重要线索。肿瘤坏死因子α (TNF α)基因位于HLA II类基因簇中。最近的研究表明，TNF α在调节人类正常睡眠中起着重要作用，在发作性睡症中该细胞因子的调节可能受到干扰。我们通过单链构象多态性（SSCP）分析在TNF α基因中寻找与发作性睡症相关的突变。12个300-500bp的PCR片段，覆盖启动子区，外显子和内含子，在两种不同的实验条件下检查两次。一种新的多态性，C-850T，在发作性睡症患者TNF α基因的启动子区域被发现。用限制性片段长度多态性法检测基因型频率。92例发作性睡病患者与91例正常对照者基因型分布无显著差异。这些结果不支持我们的假设，即TNF α产生的遗传异常是发作性睡病的病因。

The striking evidence of almost 100% association of narcolepsy with HLA DR2(DR15) antigen is an important clue to elucidate molecular basis of this sleep disorder. The gene for tumor necrosis factor alpha (TNF alpha) is located in the HLA class II gene cluster. Recent studies have indicated that TNF alpha plays an important role in regulation of normal human sleep and regulation of this cytokine may be disturbed in narcolepsy. We searched for a mutation associated with narcolepsy in the TNF alpha gene by single-strand conformation polymorphism (SSCP) analysis. Twelve PCR fragments of 300-500bp covering promoter region, exons, and introns, are examined twice at two different experimental conditions. A novel polymorphism, C-850T, was found in the promoter region of the TNF alpha gene in narcoleptic patients. Genotype frequency was examined by restriction fragment length polymorphism method. No significant difference of genotype distribution was found between 92 patients with narcolepsy and 91 normal controls. These results do not support our hypothesis that genetic abnormality of TNF alpha production is pathogenetic for narcolepsy.