PMID- 17576097
OWN - NLM
STAT- MEDLINE
DCOM- 20071113
LR  - 20180429
IS  - 1389-9457 (Print)
IS  - 1389-9457 (Linking)
VI  - 8
IP  - 5
DP  - 2007 Aug
TI  - Screening the human prepro-orexin gene in a single-centre narcolepsy cohort.
PG  - 498-502
AB  - BACKGROUND AND PURPOSE: Although the orexin system has an established role in 
      narcolepsy, the mechanism of orexin deficiency in human cases is unknown. The 
      strong association with human leukocyte antigen (HLA) DQB1*0602 suggests an 
      autoimmune basis, but supporting evidence is lacking. Although data indicate that 
      HLA status is not the sole genetic factor, only a single case of a functional 
      orexin system mutation has been discovered, in a study with a selection bias 
      designed to increase yield. In this study, we examined the prepro-orexin gene for 
      mutations in a cohort of unrelated patients with narcolepsy from a national UK 
      referral centre. PATIENTS AND METHODS: Subjects with a diagnosis of narcolepsy 
      were recruited from a patient database. DNA samples were obtained using buccal 
      smear kits. The prepro-orexin gene was amplified using polymerase chain reactions 
      and screened for polymorphisms and mutations. RESULTS: Eighty-one patients were 
      recruited, of whom 69 provided DNA samples. A previously described intronic 
      single nucleotide polymorphism, of unlikely significance, was identified in one 
      subject who had typical clinical and electrophysiological features of narcolepsy. 
      It was located 16 base pairs downstream from exon 1. No other mutations were 
      found. CONCLUSION: This result supports existing evidence which indicates that 
      mutations of the prepro-orexin gene are rare and that the genetic contribution to 
      the aetiology of human narcolepsy is likely to be complex.
FAU - Quinnell, Timothy G
AU  - Quinnell TG
AD  - Respiratory Support and Sleep Centre, Papworth Hospital, Papworth Everard, 
      Cambridgeshire, UK. tim.quinnell@papworth.nhs.uk
FAU - Farooqi, I Sadaf
AU  - Farooqi IS
FAU - Smith, Ian E
AU  - Smith IE
FAU - Shneerson, John M
AU  - Shneerson JM
LA  - eng
GR  - 068086/Wellcome Trust/United Kingdom
PT  - Journal Article
DEP - 20070618
PL  - Netherlands
TA  - Sleep Med
JT  - Sleep medicine
JID - 100898759
RN  - 0 (HLA-DQ Antigens)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Orexins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adult
MH  - Biopsy
MH  - Cheek/pathology
MH  - Cohort Studies
MH  - DNA/isolation & purification
MH  - Female
MH  - HLA-DQ Antigens/*genetics
MH  - HLA-DQ beta-Chains
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics
MH  - Male
MH  - Membrane Glycoproteins/*genetics
MH  - Microsatellite Repeats/*genetics
MH  - Narcolepsy/*genetics/pathology
MH  - Neuropeptides/*genetics
MH  - Orexins
MH  - *Polymorphism, Single Nucleotide
EDAT- 2007/06/20 09:00
MHDA- 2007/11/14 09:00
CRDT- 2007/06/20 09:00
PHST- 2006/09/05 00:00 [received]
PHST- 2006/11/13 00:00 [revised]
PHST- 2006/11/25 00:00 [accepted]
PHST- 2007/06/20 09:00 [pubmed]
PHST- 2007/11/14 09:00 [medline]
PHST- 2007/06/20 09:00 [entrez]
AID - S1389-9457(06)00708-8 [pii]
AID - 10.1016/j.sleep.2006.11.016 [doi]
PST - ppublish
SO  - Sleep Med. 2007 Aug;8(5):498-502. doi: 10.1016/j.sleep.2006.11.016. Epub 2007 Jun 
      18.