A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains

C Peyron, J Faraco, W Rogers, B Ripley, S Overeem… - Nature medicine, 2000 - nature.com
C Peyron, J Faraco, W Rogers, B Ripley, S Overeem, Y Charnay, S Nevsimalova, M Aldrich…
Nature medicine, 2000nature.com
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 …
Abstract
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.
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