Whole Exome Sequencing Identifies RAI1 Mutation in a Morbidly Obese Child Diagnosed With ROHHAD Syndrome
Vidhu V Thaker,Kristyn M. Esteves,Meghan C. Towne,Catherine A. Brownstein,Philip James,Laura Crowley,Joel N. Hirschhorn,Sarah H. Elsea,Alan H. Beggs,Jonathan Picker,Pankaj B. Agrawal +10 more
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TLDR
This case highlights the challenges in the diagnosis of ROHHAD syndrome and its potential overlap with SMS, and proposes RAI1 as a candidate gene for children with morbid obesity.Abstract:
Context: The current obesity epidemic is attributed to complex interactions between genetic and environmental factors. However, a limited number of cases, especially those with early-onset severe obesity, are linked to single gene defects. Rapid-onset obesity with hypothalamic dysfunction, hypoventilation and autonomic dysregulation (ROHHAD) is one of the syndromes that presents with abrupt-onset extreme weight gain with an unknown genetic basis. Objective: To identify the underlying genetic etiology in a child with morbid early-onset obesity, hypoventilation, and autonomic and behavioral disturbances who was clinically diagnosed with ROHHAD syndrome. Design/Setting/Intervention: The index patient was evaluated at an academic medical center. Whole-exome sequencing was performed on the proband and his parents. Genetic variants were validated by Sanger sequencing. Results: We identified a novel de novo nonsense mutation, c.3265 C>T (p.R1089X), in the retinoic acid-induced 1 (RAI1) gene in the proband. Mutat...read more
Citations
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Rare Genetic Forms of Obesity: Clinical Approach and Current Treatments in 2016.
TL;DR: In this paper, the melanocortin 4 receptor (MC4R)-linked obesity is characterized by the variable severity of obesity and no notable additional phenotypes, and specific treatments are available only for specific types of monogenic obesity, such as leptin deficiency.
Genetic and epigenetic causes of obesity.
TL;DR: The role and potential mechanism of epigenetic changes that may be involved as mediators of the environmental influences and that may provide future opportunities for intervention are discussed.
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Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea-related Quantitative Trait Locus in Men.
Han Chen,Han Chen,Brian E. Cade,Kevin J. Gleason,Kevin J. Gleason,Andrew Bjonnes,Adrienne M. Stilp,Tamar Sofer,Tamar Sofer,Matthew P. Conomos,Sonia Ancoli-Israel,Raanan Arens,Ali Azarbarzin,Graeme I. Bell,Jennifer E. Below,Jennifer E. Below,Sung Chun,Daniel S. Evans,Ralf Ewert,Alexis C. Frazier-Wood,Sina A. Gharib,José Haba-Rubio,Erika W. Hagen,Raphael Heinzer,David R. Hillman,W. Craig Johnson,Zoltán Kutalik,Zoltán Kutalik,Jacqueline M. Lane,Jacqueline M. Lane,Emma K. Larkin,Seung Ku Lee,Jingjing Liang,Jose S. Loredo,Sutapa Mukherjee,Lyle J. Palmer,George J. Papanicolaou,Thomas Penzel,Paul E. Peppard,Wendy S. Post,Alberto R. Ramos,Kenneth Rice,Jerome I. Rotter,Scott A. Sands,Neomi A. Shah,Chol Shin,Katie L. Stone,Beate Stubbe,Jae Hoon Sul,Jae Hoon Sul,Mehdi Tafti,Kent D. Taylor,Alexander Teumer,Timothy A. Thornton,Gregory J. Tranah,Chaolong Wang,Chaolong Wang,Heming Wang,Heming Wang,Simon C. Warby,D. Andrew Wellman,Phyllis C. Zee,Craig L. Hanis,Cathy C. Laurie,Daniel J. Gottlieb,Daniel J. Gottlieb,Sanjay R. Patel,Xiaofeng Zhu,Shamil R. Sunyaev,Shamil R. Sunyaev,Richa Saxena,Richa Saxena,Xihong Lin,Susan Redline +73 more
TL;DR: Gene‐by‐sex interactions in suggestive association regions are identified, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.
Journal ArticleDOI
RAI1 gene mutations: mechanisms of Smith-Magenis syndrome.
TL;DR: Patients with RAI1 pathogenic variants show some phenotypic differences when compared to those carrying the typical deletion, and these differences reflect the primary pathogenetic role of RAi1 without the pathogenic contribution of the other genes included in the typical 17p11.2 deletion.
Journal ArticleDOI
Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD): Exome sequencing of trios, monozygotic twins and tumours
Sarah F. Barclay,Casey M. Rand,Lauren A. Borch,Lisa Nguyen,Paul A. Gray,William T. Gibson,Richard J. A. Wilson,Paul M. K. Gordon,Zaw Aung,Elizabeth Berry-Kravis,Diego Ize-Ludlow,Debra E. Weese-Mayer,Debra E. Weese-Mayer,N. Torben Bech-Hansen +13 more
TL;DR: In this paper, the exomes of seven ROHHAD trios plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort) were sequenced to identify constitutional and somatic de novo sequence variants.
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Journal ArticleDOI
Mutations in RAI1 associated with Smith–Magenis syndrome
TL;DR: This work has identified dominant frameshift mutations leading to protein truncation in RAI1 in three individuals who have phenotypic features consistent with SMS but do not have 17p11.2 deletions detectable by standard fluorescence in situ hybridization techniques.
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