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

Christelle Peyron, Juliette Faraco, William Rogers, Beth Ripley, Sebastiaan Overeem, Yves Charnay, Sona Nevsimalova, Michael Aldrich, David Reynolds, Roger Albin, Robin Li, Marcel Hungs, Mario Pedrazzoli, Muralidhara Padigaru, Melanie Kucherlapati, Fan Jun, Richard Maki, Gert Jan Lammers, Constantin Bouras, Raju KucherlapatiSeiji Nishino, Emmanuel Mignot

Research output: Contribution to journalArticlepeer-review

1601 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)991-997
Number of pages7
JournalNature Medicine
Volume6
Issue number9
DOIs
StatePublished - Sep 1 2000

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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