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

被引：14

作者：

Barclay, Sarah F. ^{[1
]}

Rand, Casey M. ^{[2
,3
]}

Gray, Paul A. ^{[4
]}

Gibson, William T. ^{[5
,6
]}

Wilson, Richard J. A. ^{[7
,8
]}

Berry-Kravis, Elizabeth M. ^{[9
,10
,11
]}

Ize-Ludlow, Diego ^{[12
]}

Bech-Hansen, N. Torben ^{[1
]}

Weese-Mayer, Debra E. ^{[2
,3
,13
]}

机构：

[1] Univ Calgary, Alberta Childrens Hosp Res Inst, Cumming Sch Med, Dept Med Genet, Calgary, AB, Canada

[2] Ann & Robert H Lurie Childrens Hosp Chicago, Stanley Manne Childrens Res Inst, CAMP, Chicago, IL 60611 USA

[3] Ann & Robert H Lurie Childrens Hosp Chicago, Dept Pediat, Chicago, IL 60611 USA

[4] Washington Univ Med, Dept Anat & Neurobiol, St Louis, MO USA

[5] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada

[6] Child & Family Res Inst, Vancouver, BC, Canada

[7] Univ Calgary, Alberta Childrens Hosp Res Inst, Dept Physiol & Pharmacol, Calgary, AB, Canada

[8] Univ Calgary, Cumming Sch Med, Hotchkiss Brain Inst, Calgary, AB, Canada

[9] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA

[10] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA

[11] Rush Univ, Med Ctr, Dept Biochem, Chicago, IL 60612 USA

[12] Univ Illinois, Dept Pediat, Div Pediat Endocrinol, Chicago, IL USA

[13] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA

来源：

RESPIRATORY PHYSIOLOGY & NEUROBIOLOGY | 2016年 / 221卷

关键词：

ROHHAD; Hypocretin; Orexin; Narcolepsy; Genes; Mutations; Next-generation sequencing; Exome sequencing; Obesity; Hypoventilation; Hyothalamic dysfunction; Autonomic dysregulation; HCRT; HCRTR1; HCRTR2; RAPID-ONSET OBESITY; HYPOTHALAMIC DYSFUNCTION; AUTONOMIC DYSREGULATION; CENTRAL HYPOVENTILATION; NARCOLEPSY; OREXIN; MANIFESTATIONS; ALIGNMENT; PEPTIDES;

D O I：

10.1016/j.resp.2015.11.002

中图分类号：

Q4 [生理学];

学科分类号：

071003 ;

摘要：

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. (C) 2015 Elsevier B.V. All rights reserved.

引用

页码：59 / 63

页数：5

共 30 条

[1] An integrated map of genetic variation from 1,092 human genomes [J].

Altshuler, David M. ;

Durbin, Richard M. ;

Abecasis, Goncalo R. ;

Bentley, David R. ;

Chakravarti, Aravinda ;

Clark, Andrew G. ;

Donnelly, Peter ;

Eichler, Evan E. ;

Flicek, Paul ;

Gabriel, Stacey B. ;

Gibbs, Richard A. ;

Green, Eric D. ;

Hurles, Matthew E. ;

Knoppers, Bartha M. ;

Korbel, Jan O. ;

Lander, Eric S. ;

Lee, Charles ;

Lehrach, Hans ;

Mardis, Elaine R. ;

Marth, Gabor T. ;

McVean, Gil A. ;

Nickerson, Deborah A. ;

Schmidt, Jeanette P. ;

Sherry, Stephen T. ;

Wang, Jun ;

Wilson, Richard K. ;

Gibbs, Richard A. ;

Dinh, Huyen ;

Kovar, Christie ;

Lee, Sandra ;

Lewis, Lora ;

Muzny, Donna ;

Reid, Jeff ;

Wang, Min ;

Wang, Jun ;

Fang, Xiaodong ;

Guo, Xiaosen ;

Jian, Min ;

Jiang, Hui ;

Jin, Xin ;

Li, Guoqing ;

Li, Jingxiang ;

Li, Yingrui ;

Li, Zhuo ;

Liu, Xiao ;

Lu, Yao ;

Ma, Xuedi ;

Su, Zhe ;

Tai, Shuaishuai ;

Tang, Meifang .

NATURE, 2012, 491 (7422) :56-65

[2] Is narcolepsy a classical autoimmune disease? [J].

Arango, Maria-Teresa ;

Kivity, Shaye ;

Shoenfeld, Yehuda .

PHARMACOLOGICAL RESEARCH, 2015, 92 :6-12

[3] Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): exome sequencing of trios, monozygotic twins and tumours [J].

Barclay, Sarah F. ;

Rand, Casey M. ;

Borch, Lauren A. ;

Nguyen, Lisa ;

Gray, Paul A. ;

Gibson, William T. ;

Wilson, Richard J. A. ;

Gordon, Paul M. K. ;

Aung, Zaw ;

Berry-Kravis, Elizabeth M. ;

Ize-Ludlow, Diego ;

Weese-Mayer, Debra E. ;

Bech-Hansen, N. Torben .

ORPHANET JOURNAL OF RARE DISEASES, 2015, 10

[4] Endocrine manifestations of the rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neural tumor syndrome in childhood [J].

Bougneres, Pierre ;

Pantalone, Letitia ;

Linglart, Agnes ;

Rothenbuehler, Anya ;

Le Stunff, Catherine .

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (10) :3971-3980

[5] Narcolepsy in orexin knockout mice:: Molecular genetics of sleep regulation [J].

Chemelli, RM ;

Willie, JT ;

Sinton, CM ;

Elmquist, JK ;

Scammell, T ;

Lee, C ;

Richardson, JA ;

Williams, SC ;

Xiong, YM ;

Kisanuki, Y ;

Fitch, TE ;

Nakazato, M ;

Hammer, RE ;

Saper, CB ;

Yanagisawa, M .

CELL, 1999, 98 (04) :437-451

[6] Rapid-Onset Obesity With Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) Syndrome May Have a Hypothalamus-Periaqueductal Gray Localization [J].

Chow, Cristelle ;

Fortier, Marielle Valerie ;

Das, Lena ;

Menon, Anuradha P. ;

Vasanwala, Rashida ;

Lam, Joyce C. M. ;

Ng, Zhi Min ;

Ling, Simon Robert ;

Chan, Derrick W. S. ;

Choong, Chew Thye ;

Liew, Wendy K. M. ;

Thomas, Terrence .

PEDIATRIC NEUROLOGY, 2015, 52 (05) :521-525

[7] The hypocretins: Hypothalamus-specific peptides with neuroexcitatory activity [J].

De Lecea, L ;

Kilduff, TS ;

Peyron, C ;

Gao, XB ;

Foye, PE ;

Danielson, PE ;

Fukuhara, C ;

Battenberg, ELF ;

Gautvik, VT ;

Bartlett, FS ;

Frankel, WN ;

van den Pol, AN ;

Bloom, FE ;

Gautvik, KM ;

Sutcliffe, JG .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (01) :322-327

[8] Delineation of Late Onset Hypoventilation Associated with Hypothalamic Dysfunction Syndrome [J].

de Pontual, Loic ;

Trochet, Delphine ;

Caillat-Zucman, Sophie ;

Abou Shenab, Othman A. ;

Bougneres, Pierre ;

Crow, Yanick ;

Cunningham, Steve ;

Esteva, Blandine ;

Heberle, Lada Cindro ;

Leger, Juliane ;

Pinto, Graziella ;

Polak, Michel ;

Shafik, Magdy Helmy ;

Straus, Christian ;

Trang, Ha ;

Munnich, Arnold ;

Lyonnet, Stanislas ;

Desguerre, Isabelle ;

Amiel, Jeanne .

PEDIATRIC RESEARCH, 2008, 64 (06) :689-694

[9] Hypocretin-1 Deficiency in a Girl With ROHHAD Syndrome [J].

Dhondt, Karlien ;

Verloo, Patrick ;

Verhelst, Helene ;

Van Coster, Rudy ;

Overeem, Sebastiaan .

PEDIATRICS, 2013, 132 (03) :E788-E792

[10] PRIMARY ALVEOLAR HYPOVENTILATION SYNDROME (ONDINES CURSE) - ASSOCIATION WITH MANIFESTATIONS OF HYPOTHALMIC DISEASE [J].

FISHMAN, LS ;

SAMSON, JH ;

SPERLING, DR .

AMERICAN JOURNAL OF DISEASES OF CHILDREN, 1965, 110 (02) :155-+

← 1 2 3 →