The Experts below are selected from a list of 6339 Experts worldwide ranked by ideXlab platform
Elizabeth Berrykravis - One of the best experts on this subject based on the ideXlab platform.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation rohhad exome sequencing of trios monozygotic twins and tumours
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sarah F Barclay, Casey M Rand, Lauren Borch, Lisa Nguyen, Paul Gray, William T Gibson, Richard J A Wilson, Paul M K Gordon, Zaw Aung, Elizabeth BerrykravisAbstract:Background Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation rohhad exome sequencing of trios monozygotic twins and tumours
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sarah F Barclay, Casey M Rand, Lauren Borch, Lisa Nguyen, Paul Gray, William T Gibson, Richard J A Wilson, Paul M K Gordon, Zaw Aung, Elizabeth BerrykravisAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, Hypothalamic function, and autonomic regulation.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation analysis of Hypothalamic and autonomic candidate genes
Pediatric Research, 2011Co-Authors: Casey M Rand, Pallavi P Patwari, Richard J A Wilson, Elizabeth Berrykravis, Ekaterina Rodikova, Lili Zhou, Torben Bechhansen, Debra E WeesemayerAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Despite increased identification and advancing knowledge of the disease course, the variable onset and timing of phenotypic features in ROHHAD often result in delayed or missed diagnosis, potentially leading to fatal central hypoventilation, cardiorespiratory arrest, and impaired neurocognitive development. The 5-hydroxytryptamine receptor 1A (HTR1A), orthopedia (OTP), and pituitary adenylate cyclase activating polypeptide (PACAP) genes were targeted in the etiology of ROHHAD based on their roles in the embryologic development of the hypothalamus and autonomic nervous system. We hypothesized that variations of HTR1A, OTP, and/or PACAP would be associated with ROHHAD. All coding regions and intron-exon boundaries of the HTR1A, OTP, and PACAP genes, in addition to the promoter region of the HTR1A gene, were analyzed by standard sequencing in 25 ROHHAD cases and 25 matched controls. Thirteen variations, including six protein-changing mutations, were identified. None of these variations were significantly correlated with ROHHAD. This report provides evidence that variation of the HTR1A, OTP, and PACAP genes are not responsible for ROHHAD. These results represent a further step in the investigation of the genetic determinants of ROHHAD.
Casey M Rand - One of the best experts on this subject based on the ideXlab platform.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation rohhad exome sequencing of trios monozygotic twins and tumours
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sarah F Barclay, Casey M Rand, Lauren Borch, Lisa Nguyen, Paul Gray, William T Gibson, Richard J A Wilson, Paul M K Gordon, Zaw Aung, Elizabeth BerrykravisAbstract:Background Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation rohhad exome sequencing of trios monozygotic twins and tumours
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sarah F Barclay, Casey M Rand, Lauren Borch, Lisa Nguyen, Paul Gray, William T Gibson, Richard J A Wilson, Paul M K Gordon, Zaw Aung, Elizabeth BerrykravisAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, Hypothalamic function, and autonomic regulation.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation analysis of Hypothalamic and autonomic candidate genes
Pediatric Research, 2011Co-Authors: Casey M Rand, Pallavi P Patwari, Richard J A Wilson, Elizabeth Berrykravis, Ekaterina Rodikova, Lili Zhou, Torben Bechhansen, Debra E WeesemayerAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Despite increased identification and advancing knowledge of the disease course, the variable onset and timing of phenotypic features in ROHHAD often result in delayed or missed diagnosis, potentially leading to fatal central hypoventilation, cardiorespiratory arrest, and impaired neurocognitive development. The 5-hydroxytryptamine receptor 1A (HTR1A), orthopedia (OTP), and pituitary adenylate cyclase activating polypeptide (PACAP) genes were targeted in the etiology of ROHHAD based on their roles in the embryologic development of the hypothalamus and autonomic nervous system. We hypothesized that variations of HTR1A, OTP, and/or PACAP would be associated with ROHHAD. All coding regions and intron-exon boundaries of the HTR1A, OTP, and PACAP genes, in addition to the promoter region of the HTR1A gene, were analyzed by standard sequencing in 25 ROHHAD cases and 25 matched controls. Thirteen variations, including six protein-changing mutations, were identified. None of these variations were significantly correlated with ROHHAD. This report provides evidence that variation of the HTR1A, OTP, and PACAP genes are not responsible for ROHHAD. These results represent a further step in the investigation of the genetic determinants of ROHHAD.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation presenting in childhood
Pediatrics, 2007Co-Authors: Diego Izeludlow, Juliette Gray, Mark A Sperling, Jeff M Milunsky, Sadaf I Farooqi, Casey M RandAbstract:OBJECTIVE.The goal was to characterize the phenotype and potential candidate genes responsible for the syndrome of late-onset central hypoventilation with Hypothalamic Dysfunction. METHODS.Individuals with late-onset central hypoventilation with Hypothalamic Dysfunction who were referred to Rush University Medical Center for clinical or genetic assessment in the past 3 years were identified, and medical charts were reviewed to determine shared characteristics of the affected subjects. Blood was collected for genetic testing of candidate genes (PHOX2B, TRKB, and BDNF) and for high-resolution conventional G-banding, subtelomeric fluorescent in situ hybridization, and comparative genomic hybridization analysis. A subset of these children were studied in the Pediatric Respiratory Physiology Laboratory at Rush University Medical Center. RESULTS.Twenty-three children with what we are now naming rapid-onset obesity with Hypothalamic Dysfunction, hypoventilation, and autonomic dysregulation were identified. Comprehensive medical charts and blood for genetic testing were available for 15 children; respiratory physiology studies were performed at Rush University Medical Center on 9 children. The most characteristic manifestations were the presentation of rapid-onset obesity in the first 10 years of life (median age at onset: 3 years), followed by Hypothalamic Dysfunction and then onset of symptoms of autonomic dysregulation (median age at onset: 3.6 years) with later onset of alveolar hypoventilation (median age at onset: 6.2 years). Testing of candidate genes (PHOX2B, TRKB, and BDNF) revealed no mutations or rare variants. High-resolution chromosome analysis, comparative genomic hybridization, and subtelomeric fluorescent in situ hybridization results were negative for the 2 patients selected for those analyses. CONCLUSIONS.We provide a comprehensive description of the clinical spectrum of rapid-onset obesity with Hypothalamic Dysfunction, hypoventilation, and auto
Debra E Weesemayer - One of the best experts on this subject based on the ideXlab platform.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation analysis of Hypothalamic and autonomic candidate genes
Pediatric Research, 2011Co-Authors: Casey M Rand, Pallavi P Patwari, Richard J A Wilson, Elizabeth Berrykravis, Ekaterina Rodikova, Lili Zhou, Torben Bechhansen, Debra E WeesemayerAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Despite increased identification and advancing knowledge of the disease course, the variable onset and timing of phenotypic features in ROHHAD often result in delayed or missed diagnosis, potentially leading to fatal central hypoventilation, cardiorespiratory arrest, and impaired neurocognitive development. The 5-hydroxytryptamine receptor 1A (HTR1A), orthopedia (OTP), and pituitary adenylate cyclase activating polypeptide (PACAP) genes were targeted in the etiology of ROHHAD based on their roles in the embryologic development of the hypothalamus and autonomic nervous system. We hypothesized that variations of HTR1A, OTP, and/or PACAP would be associated with ROHHAD. All coding regions and intron-exon boundaries of the HTR1A, OTP, and PACAP genes, in addition to the promoter region of the HTR1A gene, were analyzed by standard sequencing in 25 ROHHAD cases and 25 matched controls. Thirteen variations, including six protein-changing mutations, were identified. None of these variations were significantly correlated with ROHHAD. This report provides evidence that variation of the HTR1A, OTP, and PACAP genes are not responsible for ROHHAD. These results represent a further step in the investigation of the genetic determinants of ROHHAD.
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carbon dioxide chemoreception and hypoventilation syndromes with autonomic dysregulation
Journal of Applied Physiology, 2010Co-Authors: Michael S Carroll, Pallavi P Patwari, Debra E WeesemayerAbstract:Respiratory and autonomic disorders of infancy, childhood, and adulthood are a group of disorders that have varying presentation, combined with a range of severity of respiratory control and autonomic nervous system Dysfunction. Within this group, congenital central hypoventilation syndrome and rapid onset obesity with Hypothalamic Dysfunction, hypoventilation, and autonomic dysregulation, exhibit the greatest respiratory control deficits, requiring supported ventilation as a mainstay of care. The discovery of the key role of the paired-like homeobox 2B gene in autonomic nervous system development, along with the identification of paired-like homeobox 2B gene mutations causing congenital central hypoventilation syndrome, has led to a fruitful dialog between basic scientists and physician-scientists, producing an explosion of knowledge regarding genotype-phenotype correlations in this disorder, as well as important animal models of chemosensory regulation deficit. Though the etiology of rapid onset obesity with Hypothalamic Dysfunction, hypoventilation, and autonomic dysregulation is still to be determined, recent studies have begun to carefully delineate the phenotype, suggesting that it too may provide fertile ground for research that both advances our knowledge and improves patient care.
Pallavi P Patwari - One of the best experts on this subject based on the ideXlab platform.
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Rapid-onset obesity with Hypothalamic Dysfunction, hypoventilation, and autonomic dysregulation: review and update.
Current Opinion in Pediatrics, 2014Co-Authors: Pallavi P Patwari, Lisa F. WolfeAbstract:Purpose of reviewThe focus of this review is to compare and contrast two orphan disorders of late-onset hypoventilation. Specifically, rapid-onset obesity with Hypothalamic Dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) and congenital central hypoventilation syndrome (CCHS) are d
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation analysis of Hypothalamic and autonomic candidate genes
Pediatric Research, 2011Co-Authors: Casey M Rand, Pallavi P Patwari, Richard J A Wilson, Elizabeth Berrykravis, Ekaterina Rodikova, Lili Zhou, Torben Bechhansen, Debra E WeesemayerAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Despite increased identification and advancing knowledge of the disease course, the variable onset and timing of phenotypic features in ROHHAD often result in delayed or missed diagnosis, potentially leading to fatal central hypoventilation, cardiorespiratory arrest, and impaired neurocognitive development. The 5-hydroxytryptamine receptor 1A (HTR1A), orthopedia (OTP), and pituitary adenylate cyclase activating polypeptide (PACAP) genes were targeted in the etiology of ROHHAD based on their roles in the embryologic development of the hypothalamus and autonomic nervous system. We hypothesized that variations of HTR1A, OTP, and/or PACAP would be associated with ROHHAD. All coding regions and intron-exon boundaries of the HTR1A, OTP, and PACAP genes, in addition to the promoter region of the HTR1A gene, were analyzed by standard sequencing in 25 ROHHAD cases and 25 matched controls. Thirteen variations, including six protein-changing mutations, were identified. None of these variations were significantly correlated with ROHHAD. This report provides evidence that variation of the HTR1A, OTP, and PACAP genes are not responsible for ROHHAD. These results represent a further step in the investigation of the genetic determinants of ROHHAD.
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carbon dioxide chemoreception and hypoventilation syndromes with autonomic dysregulation
Journal of Applied Physiology, 2010Co-Authors: Michael S Carroll, Pallavi P Patwari, Debra E WeesemayerAbstract:Respiratory and autonomic disorders of infancy, childhood, and adulthood are a group of disorders that have varying presentation, combined with a range of severity of respiratory control and autonomic nervous system Dysfunction. Within this group, congenital central hypoventilation syndrome and rapid onset obesity with Hypothalamic Dysfunction, hypoventilation, and autonomic dysregulation, exhibit the greatest respiratory control deficits, requiring supported ventilation as a mainstay of care. The discovery of the key role of the paired-like homeobox 2B gene in autonomic nervous system development, along with the identification of paired-like homeobox 2B gene mutations causing congenital central hypoventilation syndrome, has led to a fruitful dialog between basic scientists and physician-scientists, producing an explosion of knowledge regarding genotype-phenotype correlations in this disorder, as well as important animal models of chemosensory regulation deficit. Though the etiology of rapid onset obesity with Hypothalamic Dysfunction, hypoventilation, and autonomic dysregulation is still to be determined, recent studies have begun to carefully delineate the phenotype, suggesting that it too may provide fertile ground for research that both advances our knowledge and improves patient care.
Richard J A Wilson - One of the best experts on this subject based on the ideXlab platform.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation rohhad exome sequencing of trios monozygotic twins and tumours
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sarah F Barclay, Casey M Rand, Lauren Borch, Lisa Nguyen, Paul Gray, William T Gibson, Richard J A Wilson, Paul M K Gordon, Zaw Aung, Elizabeth BerrykravisAbstract:Background Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation rohhad exome sequencing of trios monozygotic twins and tumours
Orphanet Journal of Rare Diseases, 2015Co-Authors: Sarah F Barclay, Casey M Rand, Lauren Borch, Lisa Nguyen, Paul Gray, William T Gibson, Richard J A Wilson, Paul M K Gordon, Zaw Aung, Elizabeth BerrykravisAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is thought to be a genetic disease caused by de novo mutations, though causative mutations have yet to be identified. We searched for de novo coding mutations among a carefully-diagnosed and clinically homogeneous cohort of 35 ROHHAD patients. We sequenced the exomes of seven ROHHAD trios, plus tumours from four of these patients and the unaffected monozygotic (MZ) twin of one (discovery cohort), to identify constitutional and somatic de novo sequence variants. We further analyzed this exome data to search for candidate genes under autosomal dominant and recessive models, and to identify structural variations. Candidate genes were tested by exome or Sanger sequencing in a replication cohort of 28 ROHHAD singletons. The analysis of the trio-based exomes found 13 de novo variants. However, no two patients had de novo variants in the same gene, and additional patient exomes and mutation analysis in the replication cohort did not provide strong genetic evidence to implicate any of these sequence variants in ROHHAD. Somatic comparisons revealed no coding differences between any blood and tumour samples, or between the two discordant MZ twins. Neither autosomal dominant nor recessive analysis yielded candidate genes for ROHHAD, and we did not identify any potentially causative structural variations. Clinical exome sequencing is highly unlikely to be a useful diagnostic test in patients with true ROHHAD. As ROHHAD has a high risk for fatality if not properly managed, it remains imperative to expand the search for non-exomic genetic risk factors, as well as to investigate other possible mechanisms of disease. In so doing, we will be able to confirm objectively the ROHHAD diagnosis and to contribute to our understanding of obesity, respiratory control, Hypothalamic function, and autonomic regulation.
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rapid onset obesity with Hypothalamic Dysfunction hypoventilation and autonomic dysregulation analysis of Hypothalamic and autonomic candidate genes
Pediatric Research, 2011Co-Authors: Casey M Rand, Pallavi P Patwari, Richard J A Wilson, Elizabeth Berrykravis, Ekaterina Rodikova, Lili Zhou, Torben Bechhansen, Debra E WeesemayerAbstract:Rapid-onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) is a rare and complex pediatric disorder. Despite increased identification and advancing knowledge of the disease course, the variable onset and timing of phenotypic features in ROHHAD often result in delayed or missed diagnosis, potentially leading to fatal central hypoventilation, cardiorespiratory arrest, and impaired neurocognitive development. The 5-hydroxytryptamine receptor 1A (HTR1A), orthopedia (OTP), and pituitary adenylate cyclase activating polypeptide (PACAP) genes were targeted in the etiology of ROHHAD based on their roles in the embryologic development of the hypothalamus and autonomic nervous system. We hypothesized that variations of HTR1A, OTP, and/or PACAP would be associated with ROHHAD. All coding regions and intron-exon boundaries of the HTR1A, OTP, and PACAP genes, in addition to the promoter region of the HTR1A gene, were analyzed by standard sequencing in 25 ROHHAD cases and 25 matched controls. Thirteen variations, including six protein-changing mutations, were identified. None of these variations were significantly correlated with ROHHAD. This report provides evidence that variation of the HTR1A, OTP, and PACAP genes are not responsible for ROHHAD. These results represent a further step in the investigation of the genetic determinants of ROHHAD.