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

Sarah F. Barclay; Casey M. Rand; Paul A. Gray; William T. Gibson; Richard J.A. Wilson; Elizabeth M. Berry-Kravis; Diego Ize-Ludlow; N. Torben Bech-Hansen; Debra E. Weese-Mayer

doi:10.1016/j.resp.2015.11.002

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

Sarah F. Barclay^*, Casey M. Rand, Paul A. Gray, William T. Gibson, Richard J.A. Wilson, Elizabeth M. Berry-Kravis, Diego Ize-Ludlow, N. Torben Bech-Hansen, Debra E. Weese-Mayer

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	59-63
Number of pages	5
Journal	Respiratory Physiology and Neurobiology
Volume	221
DOIs	https://doi.org/10.1016/j.resp.2015.11.002
State	Published - Jan 15 2016

Funding

We are grateful to the families who participate in our research. Funding for the exome and Sanger sequencing was generously provided by ROHHAD Fight, Inc. S.F.B., N.T.B.H., R.J.A.W., C.M.R. and D.E.W.-M. were also funded, in part, by ROHHAD Fight, Inc. S.F.B. is also funded by the ACHRI-CIHR Training Program. N.T.B.H. is also funded by CIHR. P.A.G. is funded by NIH HL089742. R.J.A.W. is funded by AIHS and CIHR. W.T.G. is funded by the CFRI and the CIHR. Sincere thanks to Richard Pon for his assistance in designing and planning the exome sequencing experiments, to Dr. Paul Gordon for his bioinformatic assistance, and to Lauren Borch and Lisa Nguyen for their assistance with primer design and PCR amplifications for Sanger sequencing. Exome and Sanger sequencing was performed at the ACHRI Genomics and Bioinformatic Platform and UCDNA Services, University of Calgary. The authors would like to thank the Exome Aggregation Consortium and the groups that provided exome variant data for comparison. A full list of contributing groups can be found at http://exac.broadinstitute.org/about .

Keywords

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

ASJC Scopus subject areas

General Neuroscience
Physiology
Pulmonary and Respiratory Medicine

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.resp.2015.11.002

Cite this

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title = "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",

author = "Barclay, {Sarah F.} and Rand, {Casey M.} and Gray, {Paul A.} and Gibson, {William T.} and Wilson, {Richard J.A.} and Berry-Kravis, {Elizabeth M.} and Diego Ize-Ludlow and Bech-Hansen, {N. Torben} and Weese-Mayer, {Debra E.}",

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year = "2016",

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day = "15",

doi = "10.1016/j.resp.2015.11.002",

language = "English (US)",

volume = "221",

pages = "59--63",

journal = "Respiratory Physiology and Neurobiology",

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T1 - Absence of mutations in HCRT, HCRTR1 and HCRTR2 in patients with ROHHAD

AU - Barclay, Sarah F.

AU - Rand, Casey M.

AU - Gray, Paul A.

AU - Gibson, William T.

AU - Wilson, Richard J.A.

AU - Berry-Kravis, Elizabeth M.

AU - Ize-Ludlow, Diego

AU - Bech-Hansen, N. Torben

AU - Weese-Mayer, Debra E.

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N2 - 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.

AB - 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.

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KW - Hypoventilation

KW - Mutations

KW - Narcolepsy

KW - Next-generation sequencing

KW - Obesity

KW - Orexin

KW - ROHHAD

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

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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