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 M. Reynolds, Roger Albin, Robin Li, Marcel Hungs, Mario Pedrazzoli, Muralidhara Padigaru, Melanie Kucherlapati, Fan Jun, Richard Maki, Gert Jan Lammers, Constantin Bouras, Raju Kucherlapati & 2 others Seiji Nishino, Emmanuel Mignot

Research output: Contribution to journalArticle

1544 Citations (Scopus)

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 2000

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Narcolepsy
Brain
Peptides
Mutation
Gliosis
Genetic Predisposition to Disease
HLA Antigens
Radioimmunoassay
In Situ Hybridization
Screening
Inflammation
Orexins
Processing

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Peyron, C., Faraco, J., Rogers, W., Ripley, B., Overeem, S., Charnay, Y., ... Mignot, E. (2000). A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. Nature Medicine, 6(9), 991-997. https://doi.org/10.1038/79690

A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. / Peyron, Christelle; Faraco, Juliette; Rogers, William; Ripley, Beth; Overeem, Sebastiaan; Charnay, Yves; Nevsimalova, Sona; Aldrich, Michael; Reynolds, David M.; Albin, Roger; Li, Robin; Hungs, Marcel; Pedrazzoli, Mario; Padigaru, Muralidhara; Kucherlapati, Melanie; Jun, Fan; Maki, Richard; Lammers, Gert Jan; Bouras, Constantin; Kucherlapati, Raju; Nishino, Seiji; Mignot, Emmanuel.

In: Nature Medicine, Vol. 6, No. 9, 09.2000, p. 991-997.

Research output: Contribution to journalArticle

Peyron, C, Faraco, J, Rogers, W, Ripley, B, Overeem, S, Charnay, Y, Nevsimalova, S, Aldrich, M, Reynolds, DM, Albin, R, Li, R, Hungs, M, Pedrazzoli, M, Padigaru, M, Kucherlapati, M, Jun, F, Maki, R, Lammers, GJ, Bouras, C, Kucherlapati, R, Nishino, S & Mignot, E 2000, 'A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains', Nature Medicine, vol. 6, no. 9, pp. 991-997. https://doi.org/10.1038/79690
Peyron, Christelle ; Faraco, Juliette ; Rogers, William ; Ripley, Beth ; Overeem, Sebastiaan ; Charnay, Yves ; Nevsimalova, Sona ; Aldrich, Michael ; Reynolds, David M. ; Albin, Roger ; Li, Robin ; Hungs, Marcel ; Pedrazzoli, Mario ; Padigaru, Muralidhara ; Kucherlapati, Melanie ; Jun, Fan ; Maki, Richard ; Lammers, Gert Jan ; Bouras, Constantin ; Kucherlapati, Raju ; Nishino, Seiji ; Mignot, Emmanuel. / A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains. In: Nature Medicine. 2000 ; Vol. 6, No. 9. pp. 991-997.
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