title: Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD.
abstract: OBJECTIVE
  Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) is a rare pediatric disease of unknown cause. Here, in response to a recent case report describing a ROHHAD patient who suffered from secondary narcolepsy confirmed by an absence of hypocretin-1 in the cerebrospinal fluid, we consider whether the ROHHAD phenotype is owing to one or more mutations in genes specific to hypocretin protein signalling.
  
  
  METHODS
  DNA samples from 16 ROHHAD patients were analyzed using a combination of next-generation and Sanger sequencing to identify exonic sequence variations in three genes: HCRT, HCRTR1, and HCRTR2.
  
  
  RESULTS
  No rare or novel mutations were identified in the exons of HCRT, HCRTR1, or HCRTR2 genes in a set of 16 ROHHAD patients.
  
  
  CONCLUSIONS
  ROHHAD is highly unlikely to be caused by mutations in the exons of the genes for hypocretin and its two receptors.
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada. Electronic address: sarah.barclay@ucalgary.ca.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Barclay
authors.affiliation: Center for Autonomic Medicine in Pediatrics (CAMP) in Stanley Manne Children's Research Institute and in Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA. Electronic address: CRand@luriechildrens.org.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Rand
authors.affiliation: Department of Anatomy and Neurobiology, Washington University of Medicine, St. Louis, MO, USA. Electronic address: pgray@pcg.wustl.edu.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gray
authors.affiliation: Department of Medical Genetics, University of British Columbia and Child & Family Research Institute, Vancouver, BC, Canada. Electronic address: wtgibson@cfri.ubc.ca.
authors.forename: William T
authors.initials: WT
authors.lastname: Gibson
authors.affiliation: Department of Physiology and Pharmacology, Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada. Electronic address: wilsonr@ucalgary.ca.
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Wilson
authors.affiliation: Departments of Pediatrics, Neurological Sciences, and Biochemistry, Rush University Medical Center, Chicago, IL, USA. Electronic address: Elizabeth_Berry-Kravis@rush.edu.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.affiliation: Department of Pediatrics, Division of Pediatric Endocrinology at University of Illinois at Chicago, Chicago, IL, USA. Electronic address: diegoize@uic.edu.
authors.forename: Diego
authors.initials: D
authors.lastname: Ize-Ludlow
authors.affiliation: Department of Medical Genetics, Cumming School of Medicine, Alberta Children's Hospital Research Institute, University of Calgary, Calgary, AB, Canada. Electronic address: ntbech@ucalgary.ca.
authors.forename: N Torben
authors.initials: NT
authors.lastname: Bech-Hansen
authors.affiliation: Center for Autonomic Medicine in Pediatrics (CAMP) in Stanley Manne Children's Research Institute and in Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, USA; Northwestern University Feinberg School of Medicine, Chicago, IL, USA. Electronic address: D-Weese-Mayer@Northwestern.edu.
authors.forename: Debra E
authors.initials: DE
authors.lastname: Weese-Mayer
mesh_terms: D001342:Autonomic Nervous System Diseases / Q000150:complications / Q000235:genetics*; D002648:Child; D005260:Female; D006801:Humans; D007027:Hypothalamic Diseases / Q000150:complications / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D010845:Obesity Hypoventilation Syndrome / Q000150:complications / Q000235:genetics*; D064446:Orexin Receptors / Q000235:genetics*; D000068797:Orexins / Q000235:genetics*
chemical_list: C000596229:HCRT protein, human; C578630:HCRTR1 protein, human; C578626:HCRTR2 protein, human; D064446:Orexin Receptors; D000068797:Orexins
keywords: Autonomic dysregulation; Exome sequencing; Genes; HCRT; HCRTR1; HCRTR2; Hyothalamic dysfunction; Hypocretin; Hypoventilation; Mutations; Narcolepsy; Next-generation sequencing; Obesity; Orexin; ROHHAD