Medicine and Health Sciences Commons^™

High Molecular Weight Adiponectin Levels Are Inversely Associated With Adiposity In Pediatric Brain Tumor Survivors., Rebecca Ronsley, Shahrad Rod Rassekh, Adam Fleming, Brianna Empringham, William Jennings, Carol Portwine, Sarah Burrow, Shayna Zelcer, Donna L Johnston, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

While children with brain tumors are surviving at record rates, survivors are at risk of cardiovascular disease and type 2 diabetes mellitus; these conditions may be driven by excess body fat. Adiponectin in an adipokine that is inversely associated with the fat mass, and has been linked to cardiometabolic risk stratification in the general population. However, adiponectin's profile and determinants in SCBT have not been established. We tested the hypothesis that high molecular weight (HMW) adiponectin levels, the more biologically active form of adiponectin, were associated with adiposity in SCBT similarly to non-cancer controls. Seventy-four SCBT (n = 32 female) …

Medium-Term Complications Associated With Coronary Artery Aneurysms After Kawasaki Disease: A Study From The International Kawasaki Disease Registry., Brian W Mccrindle, Cedric Manlhiot, Jane W Newburger, Ashraf S Harahsheh, Therese M Giglia, Frederic Dallaire, Kevin Friedman, Tisiana Low, Kyle Runeckles, Mathew Mathew, Andrew S Mackie, Nadine F Choueiter, Pei-Ni Jone, Shelby Kutty, Anji T Yetman, Geetha Raghuveer, Elfriede Pahl, Kambiz Norozi, Kimberly E Mchugh, Jennifer S Li, Sarah D De Ferranti, Nagib Dahdah

Paediatrics Publications

Background Coronary artery aneurysms (CAAs) may occur after Kawasaki disease (KD) and lead to important morbidity and mortality. As CAA in patients with KD are rare and heterogeneous lesions, prognostication and risk stratification are difficult. We sought to derive the cumulative risk and associated factors for cardiovascular complications in patients with CAAs after KD. Methods and Results A 34-institution international registry of 1651 patients with KD who had CAAs (maximum CAA

Consensus Guidelines For Management Of Hyperammonaemia In Paediatric Patients Receiving Continuous Kidney Replacement Therapy., Rupesh Raina, Jirair K Bedoyan, Uta Lichter-Konecki, Philippe Jouvet, Stefano Picca, Nicholas Ah Mew, Marcel C Machado, Ronith Chakraborty, Meghana Vemuganti, Manpreet K Grewal, Timothy Bunchman, Sidharth Kumar Sethi, Vinod Krishnappa, Mignon Mcculloch, Khalid Alhasan, Arvind Bagga, Rajit K Basu, Franz Schaefer, Guido Filler, Bradley A Warady

Paediatrics Publications

Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the …

Osteochondritis Dissecans In Pediatric Patients With Juvenile Idiopathic Arthritis., Bradley C Jackson, Debra L Bartley, Roberta A Berard

Paediatrics Publications

No abstract provided.

Unanticipated Admissions To Paediatric Cardiac Critical Care After Cardiac Catheterisations., Erin Peebles, Michael R Miller, Lee N Benson, Tilman Humpl

Paediatrics Publications

OBJECTIVES: Cardiac catheterisation is commonly used for diagnosis and therapeutic interventions in paediatric cardiology. The inherent risk of the procedure can result in unanticipated admissions to critical care. Our goals were to provide a qualitative description of characteristics and evaluation of children admitted unexpectedly to the cardiac critical care unit (CCCU).

METHODS: A retrospective single centre review of cardiac catheterisation procedures was done between 1 January, 2003 and 30 April, 2013.

RESULTS: Of 9336 cardiac catheterisations performed, 146 (1.6%) were admitted from the catheterisation laboratory to the CCCU and met inclusion criteria. Of these 146 patients, 117 (1.3%) met criteria …

Multicenter Trial Of A Combination Probiotic For Children With Gastroenteritis., Stephen B Freedman, Sarah Williamson-Urquhart, Ken J Farion, Serge Gouin, Andrew R Willan, Naveen Poonai, Katrina Hurley, Philip M Sherman, Yaron Finkelstein, Bonita E Lee, Xiao-Li Pang, Linda Chui, David Schnadower, Jianling Xie, Marc Gorelick, Suzanne Schuh

Paediatrics Publications

Background

Gastroenteritis accounts for approximately 1.7 million visits to the emergency department (ED) by children in the United States every year. Data to determine whether the use of probiotics improves outcomes in these children are lacking.

Methods

We conducted a randomized, double-blind trial involving 886 children 3 to 48 months of age with gastroenteritis who presented to six pediatric EDs in Canada. Participants received a 5-day course of a combination probiotic product containing Lactobacillus rhamnosus R0011 and L. helveticus R0052, at a dose of 4.0×10

Results

Moderate-to-severe gastroenteritis within 14 days after enrollment occurred in 108 of 414 participants (26.1%) …

Magnetic Resonance Imaging In The Diagnosis Of White Matter Signal Abnormalities., Ravi Datar, Asuri Narayan Prasad, Keng Yeow Tay, Charles Anthony Rupar, Pavlo Ohorodnyk, Michael Miller, Chitra Prasad

Paediatrics Publications

Background White matter abnormalities (WMAs) pose a diagnostic challenge when trying to establish etiologic diagnoses. During childhood and adult years, genetic disorders, metabolic disorders and acquired conditions are included in differential diagnoses. To assist clinicians and radiologists, a structured algorithm using cranial magnetic resonance imaging (MRI) has been recommended to aid in establishing working diagnoses that facilitate appropriate biochemical and genetic investigations. This retrospective pilot study investigated the validity and diagnostic utility of this algorithm when applied to white matter signal abnormalities (WMSAs) reported on imaging studies of patients seen in our clinics. Methods The MRI algorithm was applied to …

An International Delphi Survey For The Definition Of The Variables For The Development Of New Classification Criteria For Periodic Fever Aphtous Stomatitis Pharingitis Cervical Adenitis (Pfapa)., Federica Vanoni, Silvia Federici, Jordi Antón, Karyl S Barron, Paul Brogan, Fabrizio De Benedetti, Fatma Dedeoglu, Erkan Demirkaya, Veronique Hentgen, Tilmann Kallinich, Ronald Laxer, Ricardo Russo, Natasa Toplak, Yosef Uziel, Alberto Martini, Nicolino Ruperto, Marco Gattorno, Michael Hofer

Paediatrics Publications

Background

Diagnosis of Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) is currently based on a set of criteria proposed in 1999 modified from Marshall's criteria. Nevertheless no validated evidence based set of classification criteria for PFAPA has been established so far. The aim of this study was to identify candidate classification criteria PFAPA syndrome using international consensus formation through a Delphi questionnaire survey.

Methods

A first open-ended questionnaire was sent to adult and pediatric clinicians/researchers, asking to identify the variables thought most likely to be helpful and relevant for the diagnosis of PFAPA. In a second survey, respondents …

Does Specialist Physician Supply Affect Pediatric Asthma Health Outcomes?, Guido Filler, Tom Kovesi, Erik Bourdon, Sarah Ann Jones, Laurentiu Givelichian, Cheryl Rockman-Greenberg, Jason Gilliland, Marion Williams, Elaine Orrbine, Bruno Piedboeuf

Paediatrics Publications

Background

Pediatrician and pediatric subspecialist density varies substantially among the various Canadian provinces, as well as among various states in the US. It is unknown whether this variability impacts health outcomes. To study this knowledge gap, we evaluated pediatric asthma admission rates within the 2 Canadian provinces of Manitoba and Saskatchewan, which have similarly sized pediatric populations and substantially different physician densities.

Methods

This was a retrospective cross-sectional cohort study. Health regions defined by the provincial governments, have, in turn, been classified into "peer groups" by Statistics Canada, on the basis of common socio-economic characteristics and socio-demographic determinants of health. …

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy., Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel

Paediatrics Publications

BACKGROUND: Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

METHODS: We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was …

Nusinersen Versus Sham Control In Later-Onset Spinal Muscular Atrophy, Eugenio Mercuri, Basil T Darras, Claudia A Chiriboga, John W Day, Craig Campbell, Anne M Connolly, Susan T Iannaccone, Janbernd Kirschner, Nancy L Kuntz, Kayoko Saito, Perry B Shieh, Már Tulinius, Elena S Mazzone, Jacqueline Montes, Kathie M Bishop, Qingqing Yang, Richard Foster, Sarah Gheuens, C Frank Bennett, Wildon Farwell, Eugene Schneider, Darryl C De Vivo, Richard S Finkel

Paediatrics Publications

Background

Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 ( SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA).

Methods

We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2:1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was …

Peripheral Blood Epi-Signature Of Claes-Jensen Syndrome Enables Sensitive And Specific Identification Of Patients And Healthy Carriers With Pathogenic Mutations In Kdm5c, Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

Background

Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the

Results

Genome-wide DNA methylation analysis of 7 male patients affected with Claes-Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA methylation defect (epi-signature) in the peripheral blood of these patients, including 1769 individual CpGs and 9 genomic regions. Six healthy female carriers showed less pronounced but distinctive changes in the same regions enabling their differentiation from both patients and controls. Highly specific computational model using the most significant methylation changes demonstrated 100% accuracy in differentiating patients, carriers, and controls in the training cohort, …

Canadian Guidelines For Controlled Pediatric Donation After Circulatory Determination Of Death-Summary Report, Matthew J Weiss, Laura Hornby, Bram Rochwerg, Michael Van Manen, Sonny Dhanani, V Ben Sivarajan, Amber Appleby, Mary Bennett, Daniel Buchman, Catherine Farrell, Aviva Goldberg, Rebecca Greenberg, Ram Singh, Thomas A Nakagawa, William Witteman, Jill Barter, Allon Beck, Kevin Coughlin, Alf Conradi, Cynthia Cupido, Rosanne Dawson, Anne Dipchand, Darren Freed, Karen Hornby, Valerie Langlois, Cheryl Mack, Meagan Mahoney, Deepak Manhas, Christopher Tomlinson, Samara Zavalkoff, Sam D Shemie

Paediatrics Publications

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada.

METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory …

Disparities In Rate, Triggers, And Management In Pediatric And Adult Cases Of Suspected Drug-Induced Anaphylaxis In Canada, Sofianne Gabrielli, Ann E Clarke, Harley Eisman, Judy Morris, Lawrence Joseph, Sebastien La Vieille, Peter Small, Rodrick Lim, Paul Enarson, Michal Zelcer, Edmond S Chan, Chris Mill, Moshe Ben-Shoshan

Paediatrics Publications

Introduction

Data is sparse on drug-induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children.

Objective

We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada.

Methods

Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré-Coeur with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized data form documenting the reaction …

Oral Morphine Versus Ibuprofen Administered At Home For Postoperative Orthopedic Pain In Children: A Randomized Controlled Trial, Naveen Poonai, Natasha Datoo, Samina Ali, Megan Cashin, Amy L Drendel, Rongbo Zhu, Natasha Lepore, Michael Greff, Michael Rieder, Debra Bartley

Paediatrics Publications

BACKGROUND: Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain.

METHODS: We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale …

Therapeutic And Prognostic Implications Of Braf V600e In Pediatric Low-Grade Gliomas., Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara Mckeown, Jim Loukides, Ofelia Cruz, Carmen De Torres, Cheng-Ying Ho, Roger J Packer, Ruth Tatevossian, Ibrahim Qaddoumi, Julie H Harreld, James D Dalton, Jean Mulcahy-Levy, Nicholas Foreman, Matthias A Karajannis, Shiyang Wang, Matija Snuderl, Amulya Nageswara Rao, Caterina Giannini, Mark Kieran, Keith L Ligon, Maria Luisa Garre, Paolo Nozza, Samantha Mascelli, Alessandro Raso, Sabine Mueller, Theodore Nicolaides, Karen Silva, Romain Perbet, Alexandre Vasiljevic, Cécile Faure Conter, Didier Frappaz, Sarah Leary, Courtney Crane, Aden Chan, Ho-Keung Ng, Zhi-Feng Shi, Ying Mao, Elizabeth Finch, David Eisenstat, Bev Wilson, Anne Sophie Carret, Peter Hauser, David Sumerauer, Lenka Krskova, Valerie Larouche, Adam Fleming, Shayna Zelcer, Nada Jabado, James T Rutka, Peter Dirks, Michael D Taylor, Shiyi Chen, Ute Bartels, Annie Huang, David W Ellison, Eric Bouffet, Cynthia Hawkins, Uri Tabori

Paediatrics Publications

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown.

Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180).

Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a …

Growth And Weight Gain In Children With Juvenile Idiopathic Arthritis: Results From The Reacch-Out Cohort., Jaime Guzman, Tristan Kerr, Leanne M Ward, Jinhui Ma, Kiem Oen, Alan M Rosenberg, Brian M Feldman, Gilles Boire, Kristin Houghton, Paul Dancey, Rosie Scuccimarri, Alessandra Bruns, Adam M Huber, Karen Watanabe Duffy, Natalie J Shiff, Roberta A Berard, Deborah M Levy, Elizabeth Stringer, Kimberly Morishita, Nicole Johnson, David A Cabral, Maggie Larché, Ross E Petty, Ronald M Laxer, Earl Silverman, Paivi Miettunen, Anne-Laure Chetaille, Elie Haddad, Lynn Spiegel, Stuart E Turvey, Heinrike Schmeling, Bianca Lang, Janet Ellsworth, Suzanne E Ramsey, Johannes Roth, Sarah Campillo, Susanne Benseler, Gaëlle Chédeville, Rayfel Schneider, Shirley M L Tse, Roxana Bolaria, Katherine Gross, Debbie Feldman, Bonnie Cameron, Roman Jurencak, Jean Dorval, Claire Leblanc, Claire St Cyr, Michele Gibbon, Rae S M Yeung, Ciarán M Duffy, Lori B Tucker

Paediatrics Publications

BACKGROUND: With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort.

METHODS: Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth.

RESULTS: One thousand one hundred forty seven children …

Brain Biomarkers And Pre-Injury Cognition Are Associated With Long-Term Cognitive Outcome In Children With Traumatic Brain Injury, Amy A Wilkinson, Maureen Dennis, Nevena Simic, Margot J Taylor, Benjamin R Morgan, Helena Frndova, Karen Choong, Craig Campbell, Douglas Fraser, Vicki Anderson, Anne-Marie Guerguerian, Russell Schachar, Jamie Hutchison

Paediatrics Publications

BACKGROUND: Children with traumatic brain injury (TBI) are frequently at risk of long-term impairments of attention and executive functioning but these problems are difficult to predict. Although deficits have been reported to vary with injury severity, age at injury and sex, prognostication of outcome remains imperfect at a patient-specific level. The objective of this proof of principle study was to evaluate a variety of patient variables, along with six brain-specific and inflammatory serum protein biomarkers, as predictors of long-term cognitive outcome following paediatric TBI.

METHOD: Outcome was assessed in 23 patients via parent-rated questionnaires related to attention deficit hyperactivity disorder …

Unexpected Widespread Hypophosphatemia And Bone Disease Associated With Elemental Formula Use In Infants And Children, Luisa F Gonzalez Ballesteros, Nina S Ma, Rebecca J Gordon, Leanne Ward, Philippe Backeljauw, Halley Wasserman, David R Weber, Linda A Dimeglio, Julie Gagne, Robert Stein, Declan Cody, Kimber Simmons, Paul Zimakas, Lisa Swartz Topor, Sungeeta Agrawal, Andrew Calabria, Peter Tebben, Ruth Faircloth, Erik A Imel, Linda Casey, Thomas O Carpenter

Paediatrics Publications

OBJECTIVE: Hypophosphatemia occurs with inadequate dietary intake, malabsorption, increased renal excretion, or shifts between intracellular and extracellular compartments. We noticed the common finding of amino-acid based elemental formula [EF] use in an unexpected number of cases of idiopathic hypophosphatemia occurring in infants and children evaluated for skeletal disease. We aimed to fully characterize the clinical profiles in these cases.

METHODS: A retrospective chart review of children with unexplained hypophosphatemia was performed as cases accumulated from various centres in North America and Ireland. Data were analyzed to explore any relationships between feeding and biochemical or clinical features, effects of treatment, and …

Guideline For The Prevention Of Oral And Oropharyngeal Mucositis In Children Receiving Treatment For Cancer Or Undergoing Haematopoietic Stem Cell Transplantation, Lillian Sung, Paula Robinson, Nathaniel Treister, Tina Baggott, Paul Gibson, Wim Tissing, John Wiernikowski, Jennifer Brinklow, L Lee Dupuis

Paediatrics Publications

PURPOSE: To develop an evidence-based clinical practice guideline for the prevention of oral mucositis in children (0-18 years) receiving treatment for cancer or undergoing haematopoietic stem cell transplantation (HSCT).

METHODS: The Mucositis Prevention Guideline Development Group was interdisciplinary and included internationally recognised experts in paediatric mucositis. For the evidence review, we included randomised controlled trials (RCTs) conducted in either children or adults evaluating the following interventions selected according to prespecified criteria: cryotherapy, low level light therapy (LLLT) and keratinocyte growth factor (KGF). We also examined RCTs of any intervention conducted in children. For all systematic reviews, we synthesised the occurrence …

Evaluation Of Treatment-Related Mortality Among Paediatric Cancer Deaths: A Population Based Analysis., Jason D Pole, Paul Gibson, Marie-Chantal Ethier, Tanya Lazor, Donna L Johnston, Carol Portwine, Mariana Silva, Sarah Alexander, Lillian Sung

Paediatrics Publications

BACKGROUND: Objectives were to describe the proportion of deaths due to treatment-related mortality (TRM) and to identify risk factors and probable causes of TRM among paediatric cancer deaths in a population-based cohort.

METHODS: We included children with cancer ⩽18 years diagnosed and treated in Ontario who died between January 2003 and December 2012. Deaths were identified using a provincial registry, the Pediatric Oncology Group of Ontario Networked Information System. Probable causes of TRM were described.

RESULTS: Among the 964 deaths identified, 821 were included. The median age at diagnosis was 6.6 years (range 0-18.8) and 51.8% had at least one …

Pediatric Emergency Care Capacity In A Low-Resource Setting: An Assessment Of District Hospitals In Rwanda, Celestin Hategeka, Jean Shoveller, Lisine Tuyisenge, Cynthia Kenyon, David F Cechetto, Larry D Lynd

Paediatrics Publications

BACKGROUND: Health system strengthening is crucial to improving infant and child health outcomes in low-resource countries. While the knowledge related to improving newborn and child survival has advanced remarkably over the past few decades, many healthcare systems in such settings remain unable to effectively deliver pediatric advance life support management. With the introduction of the Emergency Triage, Assessment and Treatment plus Admission care (ETAT+)-a locally adapted pediatric advanced life support management program-in Rwandan district hospitals, we undertook this study to assess the extent to which these hospitals are prepared to provide this pediatric advanced life support management. The results of …

Identification Of Epigenetic Signature Associated With Alpha Thalassemia/Mental Retardation X-Linked Syndrome, Laila C Schenkel, Kristin D Kernohan, Arran Mcbride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene

RESULTS: We performed genome-wide DNA methylation assessment of the peripheral blood samples from 18 patients with ATR-X and compared it to 210 controls. We demonstrated the evidence of a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of ATRX patients, which was corroborated by targeted bisulfite sequencing experiments. Although genomically represented, differentially methylated regions showed evidence of preferential clustering in pericentromeric and telometric chromosomal regions, areas where ATRX has multiple functions related to maintenance of heterochromatin and genomic integrity.

CONCLUSION: …