A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains
A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains
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DOI：
10.1038/79690
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发表时间：
2000-09-01
期刊：
影响因子：
82.9
通讯作者：
Mignot, E
中科院分区：
文献类型：
--
作者：
Peyron, C;Faraco, J;Mignot, E
我们通过对 6 个发作性睡病患者大脑进行组织病理学检查，并对 74 例不同人类白细胞抗原和家族史状态的患者进行 Hcrt、Hcrtr1 和 Hcrtr2 突变筛查，探讨了下丘脑分泌素在人类发作性睡病中的作用。在一个早发性嗜睡症病例中发现了一种 Hcrt 突变，该突变会损害肽的运输和加工。穹窿周围区域的原位杂交和肽放射免疫测定表明下丘脑分泌素全面丧失，在所有检查的人类病例中没有神经胶质增生或炎症迹象。尽管下丘脑分泌素基因座对遗传易感性没有显着影响，但大多数人类发作性睡病病例与下丘脑分泌素系统缺陷有关。
We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.