A novel RORA genetic variant associated with early-onset obesity and insomnia

被引：0

作者：

Ouellette, Alexie ^{[1
]}

Allain, Eric P. ^{[2
,3
,4
]}

Almaghraby, Abdullah ^{[5
]}

Bouhamdani, Dominique ^{[2
]}

Ben Amor, Mouna ^{[2
]}

机构：

[1] Dalhousie Univ, Dalhousie Med New Brunswick, St John, NB, Canada

[2] Vital Hlth Network, Dr Georges L Dumont Univ Hosp Ctr, Dept Med Genet, 330 Univ Ave, Moncton, NB E1C 2Z3, Canada

[3] Atlantic Canc Res Inst, 35 Providence St, Moncton, NB E1C 8X3, Canada

[4] Univ Moncton, New Brunswick Ctr Precis Med, Dept Chem & Biochem, Moncton, NB, Canada

[5] Dalhousie Univ, IWK Hlth Ctr, Dept Pediat Endocrinol, Halifax, NS, Canada

来源：

EUROPEAN JOURNAL OF MEDICAL GENETICS | 2025年 / 76卷

关键词：

RORA; Early-onset obesity; Insomnia; Intellectual developmental disorder with or without epilepsy or cerebellar ataxia (IDDECA); CIRCADIAN-RHYTHMS; REV-ERBS; ALPHA; REVEALS;

D O I：

10.1016/j.ejmg.2025.105028

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Retinoic acid-related orphan receptor alpha (RORA) pathogenic variants cause intellectual developmental disorder with or without epilepsy or cerebellar ataxia (IDDECA). Herein, we present a female patient with a novel heterozygous likely pathogenic RORA variant, c.484C > T p.(Arg162*), with a clinical manifestation overlapping IDDECA. The patient also presented previously undocumented symptoms, namely, early-onset obesity and insomnia. Furthermore, parental testing revealed inheritance from the mother who presented a congruent phenotype. This suggests a role for RORA in both sleep and metabolism whilst extending the phenotypic spectrum of IDDECA. Notwithstanding, more fundamental work is needed to delineate the role of RORA variants in disease.

引用

页数：4

共 19 条

[1] The orphan nuclear receptor RORα regulates circadian transcription of the mammalian core-clock Bmal1 [J].

Akashi, M ;

Takumi, T .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2005, 12 (05) :441-448

[2] Genome-wide association study of the age of onset of type 1 diabetes reveals HTATIP2 as a novel T cell regulator [J].

Cardinale, Christopher J. ;

Chang, Xiao ;

Wei, Zhi ;

Qu, Hui-Qi ;

Bradfield, Jonathan P. ;

Polychronakos, Constantin ;

Hakonarson, Hakon .

FRONTIERS IN IMMUNOLOGY, 2023, 14

[3] Agonist of RORA Attenuates Nonalcoholic Fatty Liver Progression in Mice via Up-regulation of MicroRNA 122 [J].

Chai, Chofit ;

Cox, Bryan ;

Yaish, Dayana ;

Gross, Devora ;

Rosenberg, Nofar ;

Amblard, Franck ;

Shemuelian, Zohar ;

Gefen, Maytal ;

Korach, Amit ;

Tirosh, Oren ;

Lanton, Tali ;

Link, Henrike ;

Tam, Joseph ;

Permyakova, Anna ;

Ozhan, Gunes ;

Citrin, Jonathan ;

Liao, Haixing ;

Tannous, Mirna ;

Hahn, Michal ;

Axelrod, Jonathan ;

Arretxe, Enara ;

Alonso, Cristina ;

Martinez-Arranz, Ibon ;

Betes, Pablo Ortiz ;

Safadi, Rifaat ;

Salhab, Ahmad ;

Amer, Johnny ;

Tber, Zahira ;

Mengshetti, Seema ;

Giladi, Hilla ;

Schinazi, Raymond F. ;

Galun, Eithan .

GASTROENTEROLOGY, 2020, 159 (03) :999-+

[4] The nuclear receptors Rev-erbs and RORs integrate circadian rhythms and metabolism [J].

Duez, Helene ;

Staels, Bart .

DIABETES & VASCULAR DISEASE RESEARCH, 2008, 5 (02) :82-88

[5] Enhanced endocrine response to novel environment stress and lack of corticosterone circadian rhythm in Staggerer (Rora sg/sg) mutant mice [J].

Frederic, Florence ;

Chianale, Colette ;

Oliver, Charles ;

Mariani, Jean .

JOURNAL OF NEUROSCIENCE RESEARCH, 2006, 83 (08) :1525-1532

[6] ISOFORM-SPECIFIC AMINO-TERMINAL DOMAINS DICTATE DNA-BINDING PROPERTIES OF ROR-ALPHA, A NOVEL FAMILY OF ORPHAN HORMONE NUCLEAR RECEPTORS [J].

GIGUERE, V ;

TINI, M ;

FLOCK, G ;

ONG, E ;

EVANS, RM ;

OTULAKOWSKI, G .

GENES & DEVELOPMENT, 1994, 8 (05) :538-553

[7] Dual Molecular Effects of Dominant RORA Mutations Cause Two Variants of Syndromic Intellectual Disability with Either Autism or Cerebellar Ataxia [J].

Guissart, Claire ;

Latypova, Xenia ;

Rollier, Paul ;

Khan, Tahir N. ;

Stamberger, Hannah ;

McWalter, Kirsty ;

Cho, Megan T. ;

Kjaergaard, Susanne ;

Weckhuysen, Sarah ;

Lesca, Gaetan ;

Besnard, Thomas ;

Ounap, Katrin ;

Schema, Lynn ;

Chiocchetti, Andreas G. ;

McDonald, Marie ;

de Bellescize, Julitta ;

Vincent, Marie ;

Van Esch, Hilde ;

Sattler, Shannon ;

Forghani, Irman ;

Thiffault, Isabelle ;

Freitag, Christine M. ;

Barbouth, Deborah Sara ;

Cadieux-Dion, Maxime ;

Willaert, Rebecca ;

Sacoto, Maria J. Guillen ;

Safina, Nicole P. ;

Dubourg, Christele ;

Grote, Lauren ;

Carre, Wilfrid ;

Saunders, Carol ;

Pajusalu, Sander ;

Farrow, Emily ;

Boland, Anne ;

Karlowicz, Danielle Hays ;

Deleuze, Jean-Francois ;

Wojcik, Monica H. ;

Pressman, Rena ;

Isidor, Bertrand ;

Vogels, Annick ;

Van Paesschen, Wim ;

Al-Gazali, Lihadh ;

Al Shamsi, Aisha Mohamed ;

Claustres, Mireille ;

Pujol, Aurora ;

Sanders, Stephan J. ;

Rivier, Francois ;

Leboucq, Nicolas ;

Cogne, Benjamin ;

Sasorith, Souphatta .

AMERICAN JOURNAL OF HUMAN GENETICS, 2018, 102 (05) :744-759

[8] Disruption of the nuclear hormone receptor ROR alpha in staggerer mice [J].

Hamilton, BA ;

Frankel, WN ;

Kerrebrock, AW ;

Hawkins, TL ;

FitzHugh, W ;

Kusumi, K ;

Russell, LB ;

Mueller, KL ;

vanBerkel, V ;

Birren, BW ;

Kruglyak, L ;

Lander, ES .

NATURE, 1996, 379 (6567) :736-739

[9]

Jetten Anton M, 2009, Nucl Recept Signal, V7, pe003, DOI 10.1621/nrs.07003

[10] Transcriptional profiling reveals a role for RORα in regulating gene expression in obesity-associated inflammation and hepatic steatosis [J].

Kang, Hong Soon ;

Okamoto, Kyoko ;

Takeda, Yukimasa ;

Beak, Ju Youn ;

Gerrish, Kevin ;

Bortner, Carl D. ;

DeGraff, Laura M. ;

Wada, Taira ;

Xie, Wen ;

Jetten, Anton M. .

PHYSIOLOGICAL GENOMICS, 2011, 43 (13) :818-828

← 1 2 →