Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD

• A 2013 report described a ROHHAD patient with narcolepsy and altered hypocretin-1 levels.
• We evaluated the genes encoding hypocretin and its two receptors as candidate genes for ROHHAD.
• We searched for coding mutations in 16 ROHHAD patients in HCRT, HCRTR1, and HCRTR2.
• We did not identify any potentially causative mutations.
• Mutations in HCRT, HCRTR1, and HCRTR2 are not a major cause of ROHHAD.

Background and objectivesRapid-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.MethodsDNA 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.ResultsNo rare or novel mutations were identified in the exons of HCRT, HCRTR1, or HCRTR2 genes in a set of 16 ROHHAD patients.ConclusionsROHHAD is highly unlikely to be caused by mutations in the exons of the genes for hypocretin and its two receptors.