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

Abstract

Background and objectives: 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.

Keywords: Autonomic dysregulation; Exome sequencing; Genes; HCRT; HCRTR1; HCRTR2; Hyothalamic dysfunction; Hypocretin; Hypoventilation; Mutations; Narcolepsy; Next-generation sequencing; Obesity; Orexin; ROHHAD.