DOCSLIB.ORG

Supplementary Information

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplementary Information SUPPLEMENTARY INFORMATION Functional impact of global rare copy number variation in autism spectrum disorders Dalila Pinto1, Alistair T. Pagnamenta2, Lambertus Klei3, Richard Anney4, Daniele Merico5, Regina Regan6, Judith Conroy6, Tiago R. Magalhaes7,8, Catarina Correia7,8, Brett S. Abrahams9, Joana Almeida10, Elena Bacchelli11, Gary D. Bader5, Anthony J. Bailey12, Gillian Baird13, Agatino Battaglia14, Tom Berney15,56, Nadia Bolshakova4, Sven Bölte16, Patrick F. Bolton17, Thomas Bourgeron18, Sean Brennan4, Jessica Brian19, Susan E. Bryson20, Andrew R. Carson1, Guillermo Casallo1, Jillian Casey6, Brian H.Y. Chung1, Lynne Cochrane4, Christina Corsello21, Emily L. Crawford22, Andrew Crossett23, Cheryl Cytrynbaum1, Geraldine Dawson24,25, Maretha de Jonge26, Richard Delorme27, Irene Drmic19, Eftichia Duketis16, Frederico Duque10, Annette Estes28, Penny Farrar2, Bridget A. Fernandez29, Susan E. Folstein30, Eric Fombonne31, Christine M. Freitag16, John Gilbert30, Christopher Gillberg32, Joseph T. Glessner33, Jeremy Goldberg34, Andrew Green6, Jonathan Green35, Stephen J. Guter36, Hakon Hakonarson33,37, Elizabeth A. Heron4, Matthew Hill4, Richard Holt2, Jennifer L. Howe1, Gillian Hughes4, Vanessa Hus21, Roberta Igliozzi14, Cecilia Kim33, Sabine M. Klauck38, Alexander Kolevzon39, Olena Korvatska40, Vlad Kustanovich41, Clara M. Lajonchere41, Janine A. Lamb42, Magdalena Laskawiec12, Marion Leboyer43, Ann Le Couteur15,56, Bennett L. Leventhal44,45, Anath C. Lionel1, Xiao-Qing Liu1, Catherine Lord21, Linda Lotspeich46, Sabata C. Lund22, Elena Maestrini11, William Mahoney47, Carine Mantoulan48, Christian R. Marshall1, Helen McConachie15,56, Christopher J. McDougle49, Jane McGrath4, William M. McMahon50, Alison Merikangas4, Ohsuke Migita1, Nancy J. Minshew51, Ghazala K. Mirza2, Jeff Munson52, Stanley F. Nelson53, Carolyn Noakes19, Abdul Noor54, Gudrun Nygren32, Guiomar Oliveira10, Katerina Papanikolaou55, Jeremy R. Parr56, Barbara Parrini14, Tara Paton1, Andrew Pickles57, Marion Pilorge58, Joseph Piven59, Chris P. Ponting60, David J. Posey49, Annemarie Poustka38‡, Fritz Poustka16, Aparna Prasad1, Jiannis Ragoussis2, Katy Renshaw12, Jessica Rickaby1, Wendy Roberts19, Kathryn Roeder23, Bernadette Roge48, Michael L. Rutter61, Laura J. Bierut62, John P. Rice62, Jeff Salt36, Katherine Sansom1, Daisuke Sato1, Ricardo Segurado4, Ana F. Sequeira7,8, Lili Senman19, Naisha Shah6, Val C. Sheffield63, Latha Soorya39, Inês Sousa2, Olaf Stein64, Nuala Sykes2, Vera Stoppioni65, Christina Strawbridge34, Raffaella Tancredi14, Katherine Tansey4, Bhooma Thiruvahindrapduram1, Ann P. Thompson34, Susanne Thomson22, Ana Tryfon39, John Tsiantis55, Herman Van Engeland26, John B. Vincent54, Fred Volkmar66, Simon Wallace12, Kai Wang33, Zhouzhi Wang1, Thomas H. Wassink67, Caleb Webber60, Rosanna Weksberg1, Kirsty Wing2, Kerstin Wittemeyer48, Shawn Wood3, Jing Wu23, Brian L. Yaspan22, Danielle Zurawiecki39, Lonnie Zwaigenbaum68, Joseph D. Buxbaum39*, Rita M. Cantor53*, Edwin H. Cook36*, Hilary Coon50*, Michael L. Cuccaro30*, Bernie Devlin3*, Sean Ennis6*, Louise Gallagher4*, Daniel H. Geschwind9*, Michael Gill4*, Jonathan L. Haines69*, Joachim Hallmayer46*, Judith Miller50, Anthony P. Monaco2*, John I. Nurnberger Jr49*, Andrew D. Paterson1*, Margaret A. Pericak-Vance30*, Gerard D. Schellenberg70*, Peter Szatmari34*, Astrid M. Vicente7,8*, Veronica J. Vieland64*, Ellen M. Wijsman71*, Stephen W. Scherer1,72*, James S. Sutcliffe22* & Catalina Betancur58* 1 CONTENTS A. AUTISM SPECTRUM DISORDER (ASD) SAMPLE AND CONTROL COLLECTIONS 4 ASD samples 4 Control cohorts 4 B. GENOTYPING AND DATA CLEANING 5 SNP quality control 6 Intensity quality control for CNV detection 6 C. CNV DETECTION AND QUALITY CONTROL EVALUATION 7 Pilot experiment to evaluate the quality of detected stringent CNVs 8 D. CNV VERIFICATION 9 Confirmation using computational methods 9 Experimental CNV validation 9 E. RARE CNV BURDEN ANALYSIS 11 CNV global burden analysis 11 CNV Region (CNVR) burden analysis 12 CNV-based gene association test 12 Burden analysis for genes known to be implicated in ASD and/ or ID 12 Population attributable risk 13 F. GENE-SET ENRICHMENT AND FUNCTIONAL MAP 13 Analytical synopsis 13 Deriving gene sets 14 Gene-set enrichment test 14 Cryptic bias 14 Network visualization of gene-sets enriched for deletions: functional enrichment map 15 Expanded functional map between deletion-enriched gene sets and known ASD/ID genes 15 G. SUPPLEMENTARY FIGURES AND TABLES 17 H. ACKNOWLEDGEMENTS 72 I. SUPPLEMENTARY REFERENCES 72 2 LIST OF FIGURES Figure 1. Quality control and analysis flow chart 18 Figure 2. Results from ancestry analysis using genome-wide genotype data 19 Figure 3. Global CNV measures for blood versus cell-line DNA-derived samples 20 Figure 4. Examples of CNVs overlapping ASD candidate genes or loci 21 Figure 5. Number of enriched gene-sets at different FDR q-value thresholds 25 Figure 6. Overview of all enriched gene-sets in deletions 26 Figure 7. Detailed annotation of the main enriched clusters 27 Figure 8. Control for bias in length and number of deletions 28 Figure 9. Bias control for genome proximity 30 Figure 10. Distribution of q-values per gene-set 31 Figure 11. Gene coverage between ASD and/or ID gene-sets and sets enriched for deletions 32 Figure 12. Expanded functional map with high-level of annotation detail 33 LIST OF TABLES Table 1. Quality control (QC) steps for CNV analysis of ASD cases and controls 34 Table 2. Chromosome abnormalities larger than 7.5 Mb detected during QC 35 Table 3: Summary of characteristics of stringent CNVs in cases and controls 37 Table 4. Characteristics of rare CNVs in European ASD probands and controls 38 Table 5. Global rare CNV burden analyzes with respect to CNV size and CNV rate 41 Table 6. Examples of ASD candidate genes or loci 42 Table 7. Rare CNVs confirmed experimentally 43 Table 8. Rare CNVs in 996 ASD cases 59 Table 9. List of known ASD genes, ID genes, and ASD-candidates 60 Table 10. Clinically-relevant findings 65 Table 11. Population attributable risk (PAR) 68 Table 12. Number of analyzed gene-sets in the functional map enriched for deletions 69 Table 13. List of gene-sets enriched for deletions 70 3 A. AUTISM SPECTRUM DISORDER (ASD) SAMPLE AND CONTROL COLLECTIONS ASD samples In an ongoing effort, the international Autism Genome Project (AGP) Consortium is collecting ASD families for genetic studies. The first phase of this initiative involved examining genetic linkage and chromosomal rearrangements in 1,168 families having at least two ASD individuals1. In this second phase of the project, we collected more families and genotyped them to examine copy number variation (CNV) and single nucleotide polymorphisms (SNPs) affecting risk for ASD. Here, we present the analysis of rare CNVs, which is outlined in Fig. 1 in the main text. As discussed, 1,275 ASD cases (1,256 cases with both parents) were available for genotyping for our study (Fig.1). DNA was obtained from blood (63%), buccal-swabs (10%) or cell-lines (22%) (in 5% the DNA source was not available). The Autism Diagnostic Interview-Revised (ADI-R)2 and Autism Diagnostic Observation Schedule (ADOS)3 were used for research diagnostic classification. Subjects with previously known karyotypic abnormalities or other genetic disorders associated with ASD were excluded. Our ascertainment of ASD cases was based on the following criteria. Affected subjects were grouped in three classes (strict, broad and spectrum ASD) based on proband diagnostic measures. To qualify for the strict class, affected individuals met criteria for autism on both primary instruments, the ADI-R and the ADOS. The broad class included individuals who met ADI-R criteria for autism and ADOS criteria for ASD, but not autism, or vice versa. ADI-R-based diagnostic classification of subjects as ASD followed criteria published by Risi et al.4. Specifically, individuals who almost met ADI criteria for autism were classified as ASD if (1) they met criteria on social and either communication or repetitive behavior domains; or (2) met criteria on social and within 2 points of criteria for communication, or met criteria on communication and within 2 points of social criteria, or within 1 point on both social and communication domains4. Finally, the spectrum class included all individuals who were classified as ASD on both the ADI-R and ADOS or who were not evaluated on one of the instruments but were diagnosed with autism on the other instrument. Subjects from all classifications (strict, broad, and spectrum) were included in the CNV analysis. Family-history reports were taken to inform on the family type. Multiplex (MPX) families had at least two individuals receiving validated ASDs diagnoses who were first to third degree relatives (for third degree, only considered cousins). This included families with affected dizygotic twins. Simplex (SPX) families had only one known individual with ASD in first to third (cousin) degree relatives. Families with only affected monozygotic twins were considered SPX. Unknown (UKN) families were any families that did not fall into the MPX or SPX criteria above. Given the international and multi-site nature of the project and range of chronological and mental age of the probands, a range of cognitive tests were administered, and standard scores were combined across tests to provide consolidated IQ estimates. Control cohorts Our primary considerations for selecting control groups for the genome-wide CNV comparison studies included using individuals with no obvious psychiatric history
Load more

Recommended publications
  • Childhood Cerebral X-Linked Adrenoleukodystrophy with Atypical Neuroimaging Abnormalities and a No…
    9/28/2018 Journal of Postgraduate Medicine: Childhood cerebral X-linked adrenoleukodystrophy with atypical neuroimaging abnormalities and a no… Open access journal indexed with Index Medicus & EMBASE Home | Subscribe | Feedback [Download PDF] CASE REPORT Year : 2018 | Volume : 64 | Issue : 1 | Page : 59-63 Childhood cerebral X-linked adrenoleukodystrophy with atypical neuroimaging abnormalities and a novel mutation M Muranjan1, S Karande1, S Sankhe2, S Eichler3, 1 Department of Pediatrics, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra, India 2 Department of Radiology, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra, India 3 Centogene AG, Schillingallee 68, Rostock, Germany Correspondence Address: Dr. M Muranjan Department of Pediatrics, Seth GS Medical College and KEM Hospital, Parel, Mumbai, Maharashtra India Abstract Childhood cerebral X-linked adrenoleukodystrophy (XALD) typically manifests with symptoms of adrenocortical insufficiency and a variety of neurocognitive and behavioral abnormalities. A major diagnostic clue is the characteristic neuroinflammatory parieto-occipital white matter lesions on magnetic resonance imaging. This study reports a 5-year 10-month old boy presenting with generalized skin hyperpigmentation since 3 years of age. Over the past 9 months, he had developed right-sided hemiparesis and speech and behavioral abnormalities, which had progressed over 5 months to bilateral hemiparesis. Retrospective analyses of serial brain magnetic resonance images revealed an unusual pattern of lesions involving the internal capsules, corticospinal tracts in the midbrain and brainstem, and cerebellar white matter. The clinical diagnosis of childhood cerebral adrenoleukodystrophy was confirmed by elevated basal levels of adrenocorticotropin hormone and plasma very long chain fatty acid levels. Additionally, sequencing of the ABCD1 gene revealed a novel mutation.
    [Show full text]
  • Genes in Eyecare Geneseyedoc 3 W.M
    Genes in Eyecare geneseyedoc 3 W.M. Lyle and T.D. Williams 15 Mar 04 This information has been gathered from several sources; however, the principal source is V. A. McKusick’s Mendelian Inheritance in Man on CD-ROM. Baltimore, Johns Hopkins University Press, 1998. Other sources include McKusick’s, Mendelian Inheritance in Man. Catalogs of Human Genes and Genetic Disorders. Baltimore. Johns Hopkins University Press 1998 (12th edition). http://www.ncbi.nlm.nih.gov/Omim See also S.P.Daiger, L.S. Sullivan, and B.J.F. Rossiter Ret Net http://www.sph.uth.tmc.edu/Retnet disease.htm/. Also E.I. Traboulsi’s, Genetic Diseases of the Eye, New York, Oxford University Press, 1998. And Genetics in Primary Eyecare and Clinical Medicine by M.R. Seashore and R.S.Wappner, Appleton and Lange 1996. M. Ridley’s book Genome published in 2000 by Perennial provides additional information. Ridley estimates that we have 60,000 to 80,000 genes. See also R.M. Henig’s book The Monk in the Garden: The Lost and Found Genius of Gregor Mendel, published by Houghton Mifflin in 2001 which tells about the Father of Genetics. The 3rd edition of F. H. Roy’s book Ocular Syndromes and Systemic Diseases published by Lippincott Williams & Wilkins in 2002 facilitates differential diagnosis. Additional information is provided in D. Pavan-Langston’s Manual of Ocular Diagnosis and Therapy (5th edition) published by Lippincott Williams & Wilkins in 2002. M.A. Foote wrote Basic Human Genetics for Medical Writers in the AMWA Journal 2002;17:7-17. A compilation such as this might suggest that one gene = one disease.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0281166 A1 BHATTACHARJEE Et Al
    US 20160281 166A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0281166 A1 BHATTACHARJEE et al. (43) Pub. Date: Sep. 29, 2016 (54) METHODS AND SYSTEMIS FOR SCREENING Publication Classification DISEASES IN SUBJECTS (51) Int. Cl. (71) Applicant: PARABASE GENOMICS, INC., CI2O I/68 (2006.01) Boston, MA (US) C40B 30/02 (2006.01) (72) Inventors: Arindam BHATTACHARJEE, G06F 9/22 (2006.01) Andover, MA (US); Tanya (52) U.S. Cl. SOKOLSKY, Cambridge, MA (US); CPC ............. CI2O 1/6883 (2013.01); G06F 19/22 Edwin NAYLOR, Mt. Pleasant, SC (2013.01); C40B 30/02 (2013.01); C12O (US); Richard B. PARAD, Newton, 2600/156 (2013.01); C12O 2600/158 MA (US); Evan MAUCELI, (2013.01) Roslindale, MA (US) (21) Appl. No.: 15/078,579 (57) ABSTRACT (22) Filed: Mar. 23, 2016 Related U.S. Application Data The present disclosure provides systems, devices, and meth (60) Provisional application No. 62/136,836, filed on Mar. ods for a fast-turnaround, minimally invasive, and/or cost 23, 2015, provisional application No. 62/137,745, effective assay for Screening diseases, such as genetic dis filed on Mar. 24, 2015. orders and/or pathogens, in Subjects. Patent Application Publication Sep. 29, 2016 Sheet 1 of 23 US 2016/0281166 A1 SSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSS S{}}\\93? sau36 Patent Application Publication Sep. 29, 2016 Sheet 2 of 23 US 2016/0281166 A1 &**** ? ???zzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzzz??º & %&&zzzzzzzzzzzzzzzzzzzzzzz &Sssssssssssssssssssssssssssssssssssssssssssssssssssssssss & s s sS ------------------------------ Patent Application Publication Sep. 29, 2016 Sheet 3 of 23 US 2016/0281166 A1 23 25 20 FG, 2. Patent Application Publication Sep. 29, 2016 Sheet 4 of 23 US 2016/0281166 A1 : S Patent Application Publication Sep.
    [Show full text]
  • Datasheet Inhibitors / Agonists / Screening Libraries a DRUG SCREENING EXPERT
    Datasheet Inhibitors / Agonists / Screening Libraries A DRUG SCREENING EXPERT Product Name : Glycerol Catalog Number : T4776 CAS Number : 56-81-5 Molecular Formula : C3H8O3 Molecular Weight : 92.09 Apprearence : Liquid Melting Point : 20 °C Description: Glycerol or glycerin is a colourless, odourless, viscous liquid that is sweet-tasting and mostly non-toxic. It is widely used in the food industry as a sweetener and humectant and in pharmaceutical formulations. Glycerol is an important component of triglycerides (i.e. fats and oils) and of phospholipids. Glycerol is a three-carbon substance that forms the backbone of fatty acids in fats. When the body uses stored fat as a source of energy, glycerol and fatty acids are released into the bloodstream. The glycerol component can be converted into glucose by the liver and provides energy for cellular metabolism. Normally, glycerol shows very little acute toxicity and very high oral doses or acute exposures can be tolerated. On the other hand, chronically high levels of glycerol in the blood are associated with glycerol kinase deficiency (GKD). GKD causes the condition known as hyperglycerolemia, an accumulation of glycerol in the blood and urine. There are three clinically distinct forms of GKD: infantile, juvenile, and adult. The infantile form is the most severe and is associated with vomiting, lethargy, severe developmental delay, and adrenal insufficiency. The mechanisms of glycerol toxicity in infants are not known, but it appears to shift metabolism towards chronic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy).
    [Show full text]
  • Genetic Diseases Related with Osteoporosis
    Chapter 2 Genetic Diseases Related with Osteoporosis Margarita Valdés-Flores, Leonora Casas-Avila and Valeria Ponce de León-Suárez Additional information is available at the end of the chapter http://dx.doi.org/10.5772/55546 1. Introduction Osteoporosis is a disease entity characterized by the progressive loss of bone mineral density (BMD) and the deterioration of bone microarchitecture, leading to the development of frac‐ tures. Its classification encompasses two large groups, primary and secondary osteoporosis [1]. Primary osteoporosis is the disease’s most common form and results from the progressive loss of bone mass related to aging and unassociated with other illness, a natural process in adult life; its etiology is considered multifactorial and polygenic. This form currently represents a growing worldwide health problem due in part, to the contemporary environmental condi‐ tions of modern civilization. Risk factors that are considered as “modifiable” also play an important role and include physical activity, dietary habits and eating disorders. Furthermore, there is another group of associated risk factors that are considered “non-modifiable”, including gender, age, race, a personal and/or family history of fractures that in turn, indirectly reflect the degree of genetic susceptibility to this disease [2-4]. Secondary osteoporosis encompasses a large heterogeneous group of primary conditions favoring osteoporosis development. Table 1 summarizes some of the disease entities associated to primary and secondary osteoporosis. 1.1. Genetic aspects of primary osteoporosis This form of osteoporosis results from the interaction of several environmental and genetic factors, leading to difficulties in its study. It is not easy to define the magnitude of the effect of genetic susceptibility since it is a trait determined by multiple genes whose products affect the bone phenotype; moreover, the environmental factors compromising bone mineral density are also difficult to analyze.
    [Show full text]
  • Epapyrus PDF Document
    소아과:제44권 제1호 2001년 □ 증례□ 1) Hyperglycerolemia와 Congenital Adrenal Hypoplasia, Duchenne Muscular Dystrophy가 동반된 Xp21 Contiguous Gene Deletion Syndrome 한림대학교 의과대학 춘천성심병원 소아과, University Children's Hospital*, Munich, Germany Department of Pediatrics†, Metabolic Diseases, University Medical Center Utrecht, Netherlands 신대원·허준·이홍진·박원일·이경자·신윤숙*·D.R. Sjarif†·B.T. Poll-The† A Case of Xp21 Contiguous Gene Deletion Syndrome with Hyperglycerolemia, Congenital Adrenal Hypoplasia and Duchenne Muscular Dystrophy Dae-Won Shin, M.D., Jun Huh, M.D., Hong-Jin Lee, M.D., Won-Ill Park, M.D. Kyung-Ja Lee, M.D., Yoon-Sook Shin, Ph.D.*,D.R.Sjarif,M.D.† and B.T. Poll-The, M.D.† Department of Pediatrics, College of Medicine, Hallym University, Chunchon, Korea, Universtiy Children's Hospital*, Munich, Germany, Department of Pediatrics, Metabolic Diseases†, University Medical Center Utrecht, Netherlands On Xp21 region several genes such as adrenal hypoplasia congenita(AHC) gene, glycerol kinase (GK) gene and Duchenne muscular dystrophy(DMD) gene are located contiguously. If there is a long deletion in that region, various combination of genetic defect can be occurred from one kind of genetic defect to all three kinds of genetic defect simultaneously. In caseofmorethantwo genetic defects simultaneously, we call it contiguous gene deletion syndrome. The major clinical manifestations of the Xp21 contiguous gene deletion syndrome are sum of each diseases, elec- trolyte imbalance and hyperpigmentation for adrenal hypoplasia congenita, psychomotor retardation, letharginess and convulsion for glycerol kinase deficiency and muscle weakness and hypotonia for Duchenne muscular dystrophy. Goals of the treatment are control of each disorders, glucocorticoid and mineralocorticoid for adrenal hypoplasia congenita, low fat diet and prevention of fasting and hypercatabolic status for glycerol kinase deficiency and physiotherapy for Duchenne muscular dystrophy.
    [Show full text]
  • Cholestasis and Hepatic Iron Deposition in an Infant with Complex Glycerol Kinase Deficiency Diana Montoya-Williams, MD, Meredith Mowitz, MD, MS
    Cholestasis and Hepatic Iron Deposition in an Infant With Complex Glycerol Kinase Deficiency Diana Montoya-Williams, MD, Meredith Mowitz, MD, MS We present a 6-week-old male infant with persistent hyperbilirubinemia, abstract hypertriglyceridemia, elevated creatine kinase levels, and transaminitis since the second week of life. When he developed hyperkalemia, clinical suspicion was raised for adrenal insufficiency despite hemodynamic stability. A full endocrine workup revealed nearly absent adrenocorticotropic hormone. Coupled with his persistent hypertriglyceridemia (peak of 811 mg/dL) and elevated creatine kinase levels (>20 000 U/L), his corticotropin level lead to a clinical diagnosis of complex glycerol kinase deficiency (GKD), also known as Xp21 deletion syndrome. This complex disorder encompasses the phenotype of Duchenne muscular dystrophy, GKD, and congenital adrenal hypoplasia due to the deletion of 3 contiguous genetic loci on the X chromosome. Division of Neonatology, Department of Pediatrics, Our case exemplifies the presentation of this disorder and highlights the University of Florida, Gainesville, Florida important lesson of distinguishing between adrenal hypoplasia congenita and congenital adrenal hyperplasia, as well as the sometimes subtle Dr Montoya-Williams cared for the patient and drafted the initial manuscript; Dr Mowitz cared presentation of adrenal insufficiency. To our knowledge, it is also the first for the patient and reviewed and edited the reported case of complex GKD deficiency with the additional finding of manuscript; and both authors approved the fi nal hepatic iron deposition, which may indicate a potential area for exploration manuscript and agree to be accountable for all aspects of the work. regarding the pathogenesis of liver injury and cholestasis seen in cortisol- DOI: https:// doi.
    [Show full text]
  • Pot·Pour·Ri Lipidspin Noun /,Pou Pu’Ri:/ 1
    Official Publication of the National Lipid Association pot·pour·ri LipidSpin noun /,pou pu’ri:/ 1. a mixture of dried flower petals, leaves, and spices that is used to make a room smell pleasant 2. a collection of different things1 STATINS STATINS Special Freelance Edition Featuring: Omega-3 Fatty Acid Fish Oil Dietary Supplements for Disease Management: Are They Appropriate for Patients? Also in this issue: Search for the Secondary Cause: Worth the Pause Clinical Conundrum: The Estimated LDL-C Below 40 mg/dL This issue sponsored by the National Lipid Association Special Issue 2016 visit www.lipid.org Get Certied in Lipid Management Advance Your Career Improve Patient Care Enhance Your Professional Stature and Credibility Demonstrate Your Commitment to Continued Professional Development in Dyslipidemia Testing Window Fall 2016 Testing Window September 25, 2016 - November 5, 2016 (application deadline: Friday, September 16, 2016) Applications must be postmarked by the application deadline. Pharmacists, Nurses, Physicians, Physician Assistants, Dietitians, Exercise Specialists, Industry and Research Professionals Physicians The Accreditation Council for Clinical Lipidology The only advanced certication program of its kind oers two levels to recognition: available to physicians who wish to validate their Basic Competency in Clinical Lipidology Exam: rigorous training and expertise in lipidology. For individuals with general involvement in lipidology who want to sharpen their skills and The American Board of Clinical Lipidology was knowledge in lipid management. established to assess the level of knowledge required to be certied as a Clinical Lipidologist, to Clinical Lipid Specialist Certication Program: encourage professional growth in the practice Provides an opportunity for health care of lipidology, and to enhance physician practice professionals who provide specialized care to behavior to improve the quality of patient care.
    [Show full text]
  • Chemical Properties Biological Description Solubility Information
    Data Sheet (Cat.No.T4776) Glycerol Chemical Properties CAS No.: 56-81-5 Formula： C3H8O3 Molecular Weight： 92.09 Appearance： Liquid Storage： 0-4℃ for short term (days to weeks), or -20℃ for long term (months). Biological Description Description Glycerol or glycerin is a colourless, odourless, viscous liquid that is sweet-tasting and mostly non-toxic. It is widely used in the food industry as a sweetener and humectant and in pharmaceutical formulations. Glycerol is an important component of triglycerides (i.e. fats and oils) and of phospholipids. Glycerol is a three-carbon substance that forms the backbone of fatty acids in fats. When the body uses stored fat as a source of energy, glycerol and fatty acids are released into the bloodstream. The glycerol component can be converted into glucose by the liver and provides energy for cellular metabolism. Normally, glycerol shows very little acute toxicity and very high oral doses or acute exposures can be tolerated. On the other hand, chronically high levels of glycerol in the blood are associated with glycerol kinase deficiency (GKD). GKD causes the condition known as hyperglycerolemia, an accumulation of glycerol in the blood and urine. There are three clinically distinct forms of GKD: infantile, juvenile, and adult. The infantile form is the most severe and is associated with vomiting, lethargy, severe developmental delay, and adrenal insufficiency. The mechanisms of glycerol toxicity in infants are not known, but it appears to shift metabolism towards chronic acidosis. Acidosis typically occurs when arterial pH falls below 7.35. In infants with acidosis, the initial symptoms include poor feeding, vomiting, loss of appetite, weak muscle tone (hypotonia), and lack of energy (lethargy).
    [Show full text]
  • Complex Glycerol Kinase Deficiency and Adrenocortical Insufficiency In
    J Clin Res Pediatr Endocrinol 2016;8(4):468-471 DO I: 10.4274/jcrpe.2539 Case Report Complex Glycerol Kinase Deficiency and Adrenocortical Insufficiency in Two Neonates Sabriye Korkut1, Osman Baştuğ1, Margarita Raygada2, Nihal Hatipoğlu3, Selim Kurtoğlu1,3, Mustafa Kendirci3,4, Charalampos Lyssikatos2, Constantine A. Stratakis2 1Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Neonatology, Kayseri, Turkey 2Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Section on Endocrinology and Genetics, Program on Developmental Endocrinology and Genetics and Pediatric Endocrinology Inter-institute Training Program, Bethesda, Maryland, USA 3Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Kayseri, Turkey 4Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism, Kayseri, Turkey ABS TRACT Contiguous gene deletions of chromosome Xp21 can lead to glycerol kinase deficiency and severe adrenocortical insufficiency (AI) in a male newborn among other problems. We describe our experience with two such patients who presented with dysmorphic facies, AI, and pseudo-hypertriglyceridemia. Both infants had normal serum 17-hidroxyprogesterone levels, and adrenal glands could not be observed with ultrasonography. Creatine kinase and triglyceride levels were measured to elucidate the etiology of adrenal hypoplasia and were above normal limits in both cases. Both patients required
    [Show full text]
  • Molecular Basis and Approach to Gene Cloning
    Cong. Anorn., 30: 317-333, 1990 Review Contiguous Gene Syndromes as Multiple Anomalies Syndromes: Molecular Basis and Approach to Gene Cloning Norio NIIKAWA Department of Human Genetics, Nagasaki University School of Medicine, Sakamoto- Machi 12-4, Nagasaki 852, Japan ABSTRACT Recent knowledge on molecular basis of several contiguous gene syndromes as multiple anomalies syndromes, such as Prader-Willi syndrome (PWS), Angelman syn- drome (AS), Beckwith-Wiedemann syndrome (BWS), tricho-rhino-phalageal syndrome types I (TRPS I) and I1 (TRPS I1 or LGS), and complex glycerol kinase deficiency (CGKD), are reviewed. Based on the results of DNA deletion studies and on the evi- dence for the genomic imprinting mechanism of both PWS and AS, a model for the occurrence of the two syndromes is proposed. Also, a strategy of the microdissec- tion/microcloning technique as a reverse genetics technique, i.e., direct cloning of chro- mosomal DNAs from a defined region of human chromosome, particularly for the cloning of the exostosis gene in TRPS, is presented. Key words: contiguous gene syndromes, Prader-Willi syndrome, Angelman syndrome, Beckwith-Wiedemann syndrome, tricho-rhino-phalangeal syndromes, complex glycerol kinase deficiency, genomic imprinting, microdissection/microcloning technique, reverse genetics, exostosis gene A number of congenital malformation syndromes are known. In the London Dysmorphology Data Base (Winter et al., 1987), more than 1,700 different syndromes have been registered, and most of them are genetic diseases. To understand the fundamental causes, cloning of the genes responsible for the syndromes is essentially necessary. However, although their pathogenesis has been studied, in almost all the syndromes the molecular basis remains unknown.
    [Show full text]
  • 17 Disorders of Glycerol Metabolism Katrina M
    17 Disorders of Glycerol Metabolism Katrina M. Dipple, Edward R.B. McCabe 17.1 Introduction Disorders of glycerol metabolism include complex glycerol kinase deficiency (cGKD), isolated glycerol kinase deficiency (iGKD), and glycerol intolerance syndrome (GIS) (McCabe 2001a; Dipple and McCabe 2003). Glycerol kinase deficiency (GKD), both complex and isolated, is due to deletions or mutations of the glycerol kinase (GK) gene on Xp21. GIS is less well defined and some cases are due to fructose-1,6-diphosphatase (FDP) deficiency (McCabe 2001a; Dipple and McCabe 2003; Beatty et al. 2000). The treatment of acute crises in- cludes intravenous glucose and supportive care (McCabe 2001a). The mainstay of long-term treatment remains a low-fat diet and avoidance of fasting. With cGKD, there can be associated Duchenne muscular dystrophy, adrenal hypopla- sia, congenital and mental retardation; therefore, these associated diseases must be recognized and treated, especially the adrenal insufficiency (McCabe 2001a, b; Dipple and McCabe 2003; Vilain 2001). Patients with iGKD are at risk for insulin resistance, glucose intolerance, and type II diabetes mellitus (Gaudet et al. 2000), so individuals with iGKD should be monitored carefully for dia- betes. Patients with GIS must avoid glycerol, especially in intravenous infusions (McCabe 2001a). In addition, some patients with GIS have FDP deficiency, and this must be identified and treated appropriately (McCabe 2001a; Beatty et al. 2000). Unfortunately, because disorders of glycerol metabolism are such rare and presumably underdiagnosed diseases, many patients go untreated, and we therefore do not know the efficacy of treatment (Fig. 17.1). 190 Disorders of Glycerol Metabolism GKD GIS Avoid glycerol Avoid fasting IV glucose for crises Low fat diet IV glucose for crises iGKD cGKD FDP deficiency Avoid fructose Monitor for insulin Evaluate for DMD, resistance and adrenal insufficiency diabetes and developmental delay Fig.
    [Show full text]