title: Hypocretin (orexin) neuropeptide precursor gene, HCRT, polymorphisms in early-onset narcolepsy with cataplexy.
abstract: BACKGROUND
  To test if the hypocretin (orexin) neuropeptide precursor (HCRT) gene, HCRT, mutations are implicated in the development of narcolepsy with cataplexy deficiency in young children.
  
  
  METHODS
  The entire HCRT gene and ~2000 bp promoter region was first sequenced in 181 patients and 153 controls, and rare polymorphisms including three nonsynonymous amino acid changes were identified. Next the 557 bp region of exon 2 harboring the three nonsynonymous changes was sequenced in an additional 298 early-onset subjects and in 148 control samples.
  
  
  RESULTS
  A previously known common polymorphism (rs760282) and nine rare novel polymorphisms were identified in subjects and controls without significant differences. Two nonsynonymous exon 2 substitutions (+977 H54A, +979 G55R) were detected in two subjects with early onset at 7 and 6 years, respectively, but were not found in any controls. These substitutions are not likely to vastly change peptide binding to hypocretin receptors. One additional exon 2 substitution (+1019, K68R) was found in two patients and one control. Additional sequencing that focused on exon 2 showed additional subjects and controls with the +1019 K68R polymorphism and without significant differences between the subjects and the control. Segregation of two of these three nonsynonymous single nucleotide polymorphisms (SNPs) were observed from unaffected parents to offspring.
  
  
  CONCLUSIONS
  Sequencing of a large number of early-onset narcolepsy subjects revealed three novel nonsynonymous substitutions within the preprohypocretin protein, two of which were only found in patients with early-onset narcolepsy but are not likely to be functionally significant, especially in heterozygote subjects.
authors: Department of Pulmonary Medicine, Beijing University People's Hospital, Beijing, China.
authors: Xiao Song
authors: XS
authors: Dong
authors: Su Fang
authors: SF
authors: Ma
authors: Chun Wei
authors: CW
authors: Cao
authors: Jing
authors: J
authors: Li
authors: Pei
authors: P
authors: An
authors: Long
authors: L
authors: Zhao
authors: Nan Y
authors: NY
authors: Liu
authors: Han
authors: H
authors: Yan
authors: Qing Tao
authors: QT
authors: Hu
authors: Emmanuel
authors: E
authors: Mignot
authors: Kingman P
authors: KP
authors: Strohl
authors: Zhan C
authors: ZC
authors: Gao
authors: Changqing
authors: C
authors: Zeng
authors: Fang
authors: F
authors: Han
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009290:Narcolepsy / Q000208:ethnology / Q000235:genetics*; D009479:Neuropeptides / Q000235:genetics*; D000068797:Orexins; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins