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

Nat Med. 2000 Sep;6(9):991-7. doi: 10.1038/79690.

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Brain Chemistry / genetics*
  • Carrier Proteins*
  • Cerebral Cortex / chemistry
  • European Continental Ancestry Group
  • Female
  • Genetic Testing
  • Humans
  • Hypothalamus / chemistry
  • Hypothalamus / cytology
  • Intracellular Signaling Peptides and Proteins*
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation*
  • Narcolepsy / genetics*
  • Neuropeptides / analysis
  • Neuropeptides / genetics*
  • Neurotransmitter Agents / genetics
  • Orexin Receptors
  • Orexins
  • Pons / chemistry
  • Protein Processing, Post-Translational
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide / genetics*
  • Tissue Distribution

Substances

  • Carrier Proteins
  • HCRTR1 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Neurotransmitter Agents
  • Orexin Receptors
  • Orexins
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide

Associated data

  • GENBANK/AF202078
  • GENBANK/AF202079
  • GENBANK/AF202080
  • GENBANK/AF202081
  • GENBANK/AF202082
  • GENBANK/AF202083
  • GENBANK/AF202084
  • GENBANK/AF202085
  • GENBANK/AF202086
  • GENBANK/AF202087
  • GENBANK/AF202088
  • GENBANK/AF202089
  • GENBANK/AF202090
  • GENBANK/AF202091