title: Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation: analysis of hypothalamic and autonomic candidate genes.
abstract: Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Despite increased identification and advancing knowledge of the disease course, the variable onset and timing of phenotypic features in ROHHAD often result in delayed or missed diagnosis, potentially leading to fatal central hypoventilation, cardiorespiratory arrest, and impaired neurocognitive development. The 5-hydroxytryptamine receptor 1A (HTR1A), orthopedia (OTP), and pituitary adenylate cyclase activating polypeptide (PACAP) genes were targeted in the etiology of ROHHAD based on their roles in the embryologic development of the hypothalamus and autonomic nervous system. We hypothesized that variations of HTR1A, OTP, and/or PACAP would be associated with ROHHAD. All coding regions and intron-exon boundaries of the HTR1A, OTP, and PACAP genes, in addition to the promoter region of the HTR1A gene, were analyzed by standard sequencing in 25 ROHHAD cases and 25 matched controls. Thirteen variations, including six protein-changing mutations, were identified. None of these variations were significantly correlated with ROHHAD. This report provides evidence that variation of the HTR1A, OTP, and PACAP genes are not responsible for ROHHAD. These results represent a further step in the investigation of the genetic determinants of ROHHAD.
authors.affiliation: Department of Pediatrics, Children's Memorial Hospital, Chicago, IL 60614, USA.
authors.forename: Casey M
authors.initials: CM
authors.lastname: Rand
authors.forename: Pallavi P
authors.initials: PP
authors.lastname: Patwari
authors.forename: Ekaterina A
authors.initials: EA
authors.lastname: Rodikova
authors.forename: Lili
authors.initials: L
authors.lastname: Zhou
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Berry-Kravis
authors.forename: Richard J A
authors.initials: RJ
authors.lastname: Wilson
authors.forename: Torben
authors.initials: T
authors.lastname: Bech-Hansen
authors.forename: Debra E
authors.initials: DE
authors.lastname: Weese-Mayer
mesh_terms: D001342:Autonomic Nervous System Diseases / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007027:Hypothalamic Diseases / Q000235:genetics*; D007040:Hypoventilation / Q000235:genetics*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009765:Obesity / Q000235:genetics*; D010641:Phenotype; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D013577:Syndrome
chemical_list: D018398:Homeodomain Proteins; D009419:Nerve Tissue Proteins; C490261:OTP protein, human; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D044282:Receptor, Serotonin, 5-HT1A