DOCSLIB.ORG

Mygenome Gene-Disease Reference List for Providers

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mygenome Gene-Disease Reference List for Providers myGenome Gene-Disease Reference List for Providers The Clinical Section of the myGenome test is designed to examine genes associated with a set of actionable genetic disorders. The list below shows all interpreted genes and their associated conditions/diseases. This test includes interpretation of 59 genes deemed medically actionable by the American College of Medical Genetics and Genomics*. If you have any questions, please contact us at 1 (888) 507-6619 or email [email protected]. Mode of Additional Disease Associations Clinically Actionable Disease Group Gene Clinically Actionable Disease by Gene (Sources: OMIM, GeneReviews, and/or Inheritance Genetics Home Reference) Cancer Susceptibility Hereditary Breast Hereditary Breast and Ovarian Cancer syndrome (female & Reproductive BRCA1 AD and male breast cancer, ovarian/fallopian tube, prostate, N/A Cancers (4 genes) pancreatic) Hereditary Breast and Ovarian Cancer syndrome (female Fanconi anemia type D1 (AR); • Hereditary Breast and Ovarian Cancer BRCA2 AD, AR and male breast cancer, ovarian/fallopian tube, prostate, Glioblastoma; medulloblastoma; Wilms tumor syndrome pancreatic, melanoma) (AD) Lhermitte-Duclos syndrome; macrocephaly/autism • PTEN Hamartoma Tumor syndrome PTEN Hamartoma tumor syndrome; Cowden syndrome; PTEN AD syndrome; VATER association with macrocephaly and • Li-Fraumeni syndrome Banayan-Riley-Ruvalcaba syndrome ventriculomegaly; Glioma susceptibility; meningioma Bone marrow failure syndrome; Adrenocortical carcinoma (pediatric); Basal cell carcinoma; Choroid plexus TP53 AD Li-Fraumeni syndrome papilloma; Colorectal cancer; glioma susceptibility; osteosarcoma Familial Adenomatous Polyposis (FAP); Attenuated FAP; Hereditary Gastrointestinal Polyposis APC AD N/A Gardner syndrome; Turcot syndrome and Cancer (9 genes) BMPR1A AD Juvenile Polyposis syndrome Hereditary Mixed Polyposis syndrome Hereditary Non-Polyposis Colorectal syndrome (HNPCC) • Lynch syndrome Constitutional Mismatch Repair Deficiency (CMMR) MLH1 AD, AR (AD); also known as Lynch syndrome and/or Muir-Torre syndrome (AR) • Familial Adenomatous Polyposis syndrome (AD) • MUTYH-Associated Polyposis Hereditary Non-Polyposis Colorectal syndrome (HNPCC) Constitutional Mismatch Repair Deficiency (CMMR) MSH2 AD, AR (AD); also known as Lynch syndrome and/or Muir-Torre • Juvenile Polyposis syndrome (AR) • Peutz-Jeghers syndrome syndrome (AD) Hereditary Non-Polyposis Colorectal syndrome (HNPCC) Constitutional Mismatch Repair Deficiency (CMMR) MSH6 AD, AR (AD); also known as Lynch syndrome and/or Muir-Torre syndrome (AR) syndrome (AD) MUTYH-Associated Polyposis (AR; aka also known as MYH-Associated Polyposis); Adenomas, multiple MUTYH AR, AD Susceptibility to colorectal cancer (AD) colorectal, FAP type 2; Autosomal Recessive Colorectal adenomatous polyposis with pilomatricomas Hereditary Non-Polyposis Colorectal syndrome (HNPCC) Constitutional Mismatch Repair Deficiency (CMMR) PMS2 AD, AR (AD); also known as Lynch syndrome and/or Muir-Torre syndrome (AR) syndrome (AD) SMAD4 AD Juvenile Polyposis syndrome Hereditary Hemorrhagic Telangiectasia; Myrhe syndrome STK11 AD Peutz-Jeghers syndrome N/A Neurocutaneous and Ocular (4 genes) NF2 AD Neurofibromatosis type 2 N/A RB1 AD Retinoblastoma N/A • Neurofibromatosis Types 1 & 2 TSC1 AD, Unknown Tuberous Sclerosis Complex type 1 (AD) Lymphangioleiomyomatosis (Unknown) • Tuberous Sclerosis Complex Types 1 & 2 • Retinoblastoma TSC2 AD Tuberous Sclerosis Complex type 2 N/A Neuro/endocrine and Renal (8 genes) MEN1 AD, Unknown Multiple Endocrine Neoplasia type 1 (AD) Lung carcinoid (Unknown) Multiple Endocrine Neoplasia Type IIA and IIB; Pheochromocytoma; Central hypoventilation syndrome, • Familial Medullary Thyroid cancer RET AD Familial Medullary Thyroid Cancer (FMTC) • Hereditary Paraganglioma- congenital; Susceptibility to and protection against Hirschsprung disease Pheochromocytoma syndrome SDHAF2 AD Hereditary Paraganglioma-Pheochromocytoma Syndrome N/A • Multiple Endocrine Neoplasia SDHB AD Hereditary Paraganglioma-Pheochromocytoma Syndrome Cowden syndrome; Gastrointestinal stromal tumor (GIST) Types 1 & 2 SDHC AD Hereditary Paraganglioma-Pheochromocytoma Syndrome Cowden syndrome; Gastrointestinal stromal tumor (GIST) Hereditary Paraganglioma-Pheochromocytoma Syndrome Gastrointestinal stromal tumor (GIST; AD); Cowden • von Hippel-Lindau syndrome SDHD AD, AR • WT1-related Wilm's Tumor (AD) syndrome (AD); mitochondrial complex II deficiency (AR) VHL AD, AR von Hippel-Lindau Syndrome (AD) Familial erythrocytosis (AR) WAGR syndrome (Wilms tumor, aniridia, genital anomalies, retardation; AD); Denys-Drash syndrome WT1 AD, Unknown, AR WT1-related Wilm's tumor (AD) (AD); Frasier syndrome (AD); Congenital nephrotic syndrome (AD); Meacham syndrome (AR, Unknown) Cardiac Disease Cardiomyopathy (16 genes) Dilated cardiomyopathy; ACTC1 AD Hypertrophic cardiomyopathy; Atrial septal defect; restrictive cardiomyopathy • Hypertrophic Cardiomyopathy Left ventricular noncompaction Arrhythmogenic right ventricular dysplasia 11 with mild DSC2 AD, AR Arrythmogenic right ventricular cardiomyopathy (AD, AR) • Dilated Cardiomyopathy palmoplantar keratoderma and woolly hair (AR, AD) • Arrhythmogenic Right Ventricular Arrhythmogenic right ventricular dysplasia 10 (AD) DSG2 AD, AR, Unknown Dilated cardiomyopathy (Unknown) Cardiomyopathy Arrthythmogenic right ventriuclar cardiomyopathy (AR) • Left Ventricular Non-Compaction Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis (AD); Dilated cardiomyopathy with woolly hair and keratoderma Arrythmogenic right ventricular cardiomyopathy (AD); DSP AD, AR, Unknown (AR); Lethal acantholytic epidermolysis bullosa (AR); Skin Dilated cardiomyopathy (Unknown) fragility-woolly hair syndrome (AR); Keratosis palmoplantaris striata II (Unknown) GLA XL Hypertrophic cardiomyopathy (XL) Fabry disease (XL) Congenital muscular dystrophy (AD); Limb-girdle muscular dystrophy, type 1B (AD); Heart-hand syndrome, Slovenian type (AD); Lipodystrophy, familial partial, type 2 Dilated cardiomyopathy (AD) (AD); Malouf syndrome (AD); Emery-Dreifuss muscular LMNA AD, AR dystrophy (AD, AR); Hutchinson-Gilford progeria (AD, AR); Charcot-Marie-Tooth disease, type 2B1 (AR); Mandibuloacral dysplasia (AR); Restrictive dermopathy, lethal (AR) Dilated cardiomyopathy; MYBPC3 AD Hypertrophic cardiomyopathy; N/A Left ventricular noncompaction Dilated cardiomyopathy (AD); Laing distal myopathy (AD); Scapuloperoneal syndrome, MYH7 AD, AR Hypertrophic cardiomyopathy (AD); myopathic type (AD); Myosin storage myopathy (AD,AR) Left ventricular noncompaction (AD) MYL2 AD Hypertrophic cardiomyopathy N/A MYL3 AD Hypertrophic cardiomyopathy N/A PKP2 AD Arrythmogenic right ventricular cardiomyopathy N/A Glycogen storage disease of heart, lethal congenital; PRKAG2 AD Hypertrophic cardiomyopathy Wolff-Parkinson-White syndrome TMEM43 AD Arrhythmogenic right ventricular cardiomyopathy Emery-Dreifuss muscular dystrophy Dilated cardiomyopathy (AR, Unknown); TNNI3 AD, AR, Unknown Familial restrictive cardiomyopathy (AD) Hypertrophic cardiomyopathy (AD) Dilated cardiomyopathy; TNNT2 AD Hypertrophic cardiomyopathy; Familial restrictive cardiomyopathy (AD) Left ventricular noncompaction Dilated cardiomyopathy; TPM1 AD Hypertrophic cardiomyopathy; N/A Left ventricular noncompaction myGenome by Veritas - Provider Gene-Disease v1 List Apr.24.2020 Page 1 of 3 Mode of Additional Disease Associations Clinically Actionable Disease Group* Gene Clinically Actionable Disease by Gene (Sources: OMIM, GeneReviews, and/or Inheritance Genetics Home Reference) Channelopathy and Arrhythmia Long QT syndrome (AD); Atrial fibrillation, familial (AD); KCNQ1 AD, AR N/A (4 genes) Short QT syndrome (AD); Jervell and Lange-Nielsen syndrome (AR) • Romano-Ward Long QT syndromes Long QT syndrome (AD); Heart block (progressive and nonprogressive), type IA Types 1, 2, and 3 Brugada syndrome (AD); (AD); Sick sinus syndrome (AR); Susceptibility to Sudden SCN5A AD, AR, Unknown • Brugada syndrome Atrial fibrillation, familial (AD); Infant Death Syndrome (AR): Ventricular fibrillation, • Catecholaminergic Polymorphic Dilated cardiomyopathy (AD) familial (Unknown) Long QT syndrome (AD); KCNH2 AD, Unknown N/A Ventricular Tachycardia Short QT syndrome (Unknown) Catecholaminergic polymorphic ventricular tachycardia; RYR2 AD N/A Arrythmogenic right ventricular cardiomyopathy Familial Hypercholesterolemia APOB AD, AR Familial hypercholesterolemia (AD) Hypobetalipoproteinemia (AR) (3 genes) LDLR AD Familial hypercholesterolemia N/A PCSK9 AD Familial hypercholesterolemia N/A Connective Tissue Moyamoya disease; Multisystemic smooth muscle Marfan syndrome, Loeys-Dietz ACTA2 AD Familial thoracic aortic aneurysm dysfunction syndrome syndromes, and Familial Thoracic Acromicric dysplasia (AD); familial ectopia lentis (AD); Aortic Aneurysms and Dissections geleophysic dysplasia (AD); Marfan lipodystrophy FBN1 AD, Unknown Marfan syndrome (AD) (6 genes) syndrome (AD); stiff skin syndrome (AD); Weill- Marchesani syndrome (AD); MASS syndrome (Unknown) MYH11 AD Familial thoracic aortic aneurysm N/A SMAD3 AD Loeys-Dietz syndrome N/A Susceptibility to multiple self-healing squamous TGFBR1 AD Loeys-Dietz syndrome epithelioma TGFBR2 AD Loeys-Dietz syndrome Colorectal cancer, hereditary nonpolyposis Ehlers-Danlos syndrome, vascular type COL3A1 AD Ehlers-Danlos syndrome, vascular type N/A Other Actionable Diseases Malignant Hyperthermia Susceptibility CACNA1S AD Malignant hyperthermia susceptibility Hypokalemic periodic paralysis
Load more

Recommended publications
  • Prioritization of Variants Detected by Next Generation Sequencing According to the Mutation Tolerance and Mutational Architecture of the Corresponding Genes
    International Journal of Molecular Sciences Review Prioritization of Variants Detected by Next Generation Sequencing According to the Mutation Tolerance and Mutational Architecture of the Corresponding Genes Iria Roca, Ana Fernández-Marmiesse, Sofía Gouveia, Marta Segovia and María L. Couce * Unit of Diagnosis and Treatment of Congenital Metabolic Diseases, Department of Pediatrics, Hospital Clínico Universitario de Santiago de Compostela, 15706 Santiago de Compostela, Spain; [email protected] (I.R.); [email protected] (A.F.-M.); sofi[email protected] (S.G.); [email protected] (M.S.) * Correspondence: [email protected]; Tel.: +34-981-950-102 Received: 3 April 2018; Accepted: 23 May 2018; Published: 27 May 2018 Abstract: The biggest challenge geneticists face when applying next-generation sequencing technology to the diagnosis of rare diseases is determining which rare variants, from the dozens or hundreds detected, are potentially implicated in the patient’s phenotype. Thus, variant prioritization is an essential step in the process of rare disease diagnosis. In addition to conducting the usual in-silico analyses to predict variant pathogenicity (based on nucleotide/amino-acid conservation and the differences between the physicochemical features of the amino-acid change), three important concepts should be borne in mind. The first is the “mutation tolerance” of the genes in which variants are located. This describes the susceptibility of a given gene to any functional mutation and depends on the strength of purifying selection acting against it. The second is the “mutational architecture” of each gene. This describes the type and location of mutations previously identified in the gene, and their association with different phenotypes or degrees of severity.
    [Show full text]
  • Novel Association of Hypertrophic Cardiomyopathy, Sensorineural Deafness, and a Mutation in Unconventional Myosin VI (MYO6)
    309 LETTER TO JMG J Med Genet: first published as 10.1136/jmg.2003.011973 on 1 April 2004. Downloaded from Novel association of hypertrophic cardiomyopathy, sensorineural deafness, and a mutation in unconventional myosin VI (MYO6) S A Mohiddin, Z M Ahmed, A J Griffith, D Tripodi, T B Friedman, L Fananapazir, R J Morell ............................................................................................................................... J Med Genet 2004;41:309–314. doi: 10.1136/jmg.2003.011973 amilial hypertrophic cardiomyopathy (FHC) is typically Key points characterised by left ventricular hypertrophy, diastolic Fdysfunction, and hypercontractility, and is often asso- ciated with disabling symptoms, arrhythmias, and sudden N Familial hypertrophic cardiomyopathy (FHC) is typi- death.1 FHC shows both non-allelic and allelic genetic cally confined to a cardiac phenotype and is caused by heterogeneity, and results from any one of more than 100 mutations in genes encoding sarcomeric proteins. mutations in genes encoding sarcomeric proteins.2 Identified Occasionally FHC may be one component of a genes include those encoding b myosin heavy chain, the hereditary multisystem disorder. myosin regulatory and essential light chains, myosin bind- N Sensorineural hearing loss is genetically heteroge- ing protein C, troponin I, troponin C, a cardiac actin, and neous. Mutations in the MYO6 gene, encoding 23 titin. The FHC phenotype is characterised by hypertrophy, unconventional myosin VI, have been found to cause myocyte disarray and fibrosis, and results from the dominant non-syndromic sensorineural hearing loss—that is, negative expression of one of these (mainly missense) sensorineural hearing loss in the absence of any other mutations. The resulting sarcomeric dysfunction leads related clinical features. ultimately, through mechanisms that remain obscure, to pathological left ventricular remodelling.
    [Show full text]
  • Clinical Genetics and the Hutterite Brethren
    Clinical Genetics and the Hutterite Brethren: What have we learned in the new millenium? Or: A Micheil Innes MD FRCPC FCCMG Adapted from: Medical Genetics Grand Rounds January 2013 History and Population Hutterite Population Today >40 000 in AB, 30000 MB, ND, SD 1593-1770 1874-1879 25000 Transylvania 1256 migrated to American Prairies 20000 15000 World War I 10000 1565-1592 1770 - 1870 Migration to Canada Moravia5000 Ukraine 0 1500s 1520 1540 1550 1570 1580 1590 1610 1620 1680 1750 1760 1840 1860 1890 1900 1950 1975 1990 Tyrolean Alps Why Identify Genes in this Population? • Direct Benefits to • Benefit to Larger Patients/Families population – Non-invasive – Most of these disorders diagnostic test are not confined to this – Carrier test (*marriage population restrictions) – May allow for diagnosis – ?Prenatal testing of atypical cases – Enhanced understanding of – Expand basic science disease may facilitate and clinical knowledge management or treatment Initial Presentations May be Non-Specific Highlighting Importance of Careful Syndrome Delineation and Early Genetic Diagnosis • Hearing Loss – Autosomal recessive non-syndromic hearing loss (> 2loci) – Usher syndrome (> 2loci) – HDR syndrome • Cerebellar Ataxia – Joubert syndrome – DES syndrome – DCMA syndrome – CASS syndrome • Muscular Dystrophy/ High CK – LGMD2H – LGDM2I – AR EDMD – Myopathy with CPEO – Microcephaly with Chorea Genetic services and the Hutterites Religion/Culture • Has posed little barrier overall • Very accepting of medical care and technology • Although they believe that God plays a day to day role in guiding their lives, most couples accept genetic explanations for their children’s disorders • Some leuts and individual colonies are more conservative than others • Colony leader is clearly the Minister • Who speaks for the overall community when it comes to community wide issues? – e.g.
    [Show full text]
  • Splicing-Correcting Therapeutic Approaches for Retinal Dystrophies: Where Endogenous Gene Regulation and Specificity Matter
    New Developments Splicing-Correcting Therapeutic Approaches for Retinal Dystrophies: Where Endogenous Gene Regulation and Specificity Matter Niccolo` Bacchi,1 Simona Casarosa,1,2 and Michela A. Denti1,3 1Centre for Integrative Biology (CIBIO) - University of Trento, Trento, Italy 2Neuroscience Institute - National Research Council (CNR), Pisa, Italy 3Neuroscience Institute - National Research Council (CNR), Padova, Italy Correspondence: Simona Casarosa, Splicing is an important and highly regulated step in gene expression. The ability to modulate Centre for Integrative Biology it can offer a therapeutic option for many genetic disorders. Antisense-mediated splicing- (CIBIO) - University of Trento, Via correction approaches have recently been successfully exploited for some genetic diseases, Sommarive 9, 38123 Trento, Italy; and are currently demonstrating safety and efficacy in different clinical trials. Their [email protected]. application for the treatment of retinal dystrophies could potentially solve a vast panel of Michela A. Denti, Centre for Inte- grative Biology (CIBIO) - University cases, as illustrated by the abundance of mutations that could be targeted and the versatility of ofTrento,ViaSommarive9,38123 the technique. In this review, we will give an insight of the different therapeutic strategies, Trento, Italy; focusing on the current status of their application for retinal dystrophies. [email protected]. Keywords: splicing correction, antisense oligonucleotides, retinal dystrophy, gene therapy SC and MAD contributed equally to the work presented here and should therefore be regarded as equivalent authors. Submitted: April 8, 2014 Accepted: April 11, 2014 Citation: Bacchi N, Casarosa S, Denti MA. Splicing-correcting therapeutic approaches for retinal dystrophies: where endogenous gene regulation and specificity matter. Invest Oph- thalmol Vis Sci.
    [Show full text]
  • Lamin A/C Cardiomyopathy: Implications for Treatment
    Current Cardiology Reports (2019) 21:160 https://doi.org/10.1007/s11886-019-1224-7 MYOCARDIAL DISEASE (A ABBATE AND G SINAGRA, SECTION EDITORS) Lamin A/C Cardiomyopathy: Implications for Treatment Suet Nee Chen1 & Orfeo Sbaizero1,2 & Matthew R. G. Taylor1 & Luisa Mestroni1 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Purpose of Review The purpose of this review is to provide an update on lamin A/C (LMNA)-related cardiomyopathy and discuss the current recommendations and progress in the management of this disease. LMNA-related cardiomyopathy, an inherited autosomal dominant disease, is one of the most common causes of dilated cardiomyopathy and is characterized by steady progression toward heart failure and high risks of arrhythmias and sudden cardiac death. Recent Findings We discuss recent advances in the understanding of the molecular mechanisms of the disease including altered cell biomechanics, which may represent novel therapeutic targets to advance the current management approach, which relies on standard heart failure recommendations. Future therapeutic approaches include repurposed molecularly directed drugs, siRNA- based gene silencing, and genome editing. Summary LMNA-related cardiomyopathy is the focus of active in vitro and in vivo research, which is expected to generate novel biomarkers and identify new therapeutic targets. LMNA-related cardiomyopathy trials are currently underway. Keywords Lamin A/C gene . Laminopathy . Heart failure . Arrhythmias . Mechanotransduction . P53 . CRISPR–Cas9 therapy Introduction functions, including maintaining nuclear structural integrity, regulating gene expression, mechanosensing, and Mutations in the lamin A/C gene (LMNA)causelaminopathies, mechanotransduction through the lamina-associated proteins a heterogeneous group of inherited disorders including muscu- [6–11].
    [Show full text]
  • Cardiomyopathy Precision Panel Overview Indications
    Cardiomyopathy Precision Panel Overview Cardiomyopathies are a group of conditions with a strong genetic background that structurally hinder the heart to pump out blood to the rest of the body due to weakness in the heart muscles. These diseases affect individuals of all ages and can lead to heart failure and sudden cardiac death. If there is a family history of cardiomyopathy it is strongly recommended to undergo genetic testing to be aware of the family risk, personal risk, and treatment options. Most types of cardiomyopathies are inherited in a dominant manner, which means that one altered copy of the gene is enough for the disease to present in an individual. The symptoms of cardiomyopathy are variable, and these diseases can present in different ways. There are 5 types of cardiomyopathies, the most common being hypertrophic cardiomyopathy: 1. Hypertrophic cardiomyopathy (HCM) 2. Dilated cardiomyopathy (DCM) 3. Restrictive cardiomyopathy (RCM) 4. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) 5. Isolated Left Ventricular Non-Compaction Cardiomyopathy (LVNC). The Igenomix Cardiomyopathy Precision Panel serves as a diagnostic and tool ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes. Indications The Igenomix Cardiomyopathy Precision Panel is indicated in those cases where there is a clinical suspicion of cardiomyopathy with or without the following manifestations: - Shortness of breath - Fatigue - Arrythmia (abnormal heart rhythm) - Family history of arrhythmia - Abnormal scans - Ventricular tachycardia - Ventricular fibrillation - Chest Pain - Dizziness - Sudden cardiac death in the family 1 Clinical Utility The clinical utility of this panel is: - The genetic and molecular diagnosis for an accurate clinical diagnosis of a patient with personal or family history of cardiomyopathy, channelopathy or sudden cardiac death.
    [Show full text]
  • WES Gene Package Multiple Congenital Anomalie.Xlsx
    Whole Exome Sequencing Gene package Multiple congenital anomalie, version 5, 1‐2‐2018 Technical information DNA was enriched using Agilent SureSelect Clinical Research Exome V2 capture and paired‐end sequenced on the Illumina platform (outsourced). The aim is to obtain 8.1 Giga base pairs per exome with a mapped fraction of 0.99. The average coverage of the exome is ~50x. Duplicate reads are excluded. Data are demultiplexed with bcl2fastq Conversion Software from Illumina. Reads are mapped to the genome using the BWA‐MEM algorithm (reference: http://bio‐bwa.sourceforge.net/). Variant detection is performed by the Genome Analysis Toolkit HaplotypeCaller (reference: http://www.broadinstitute.org/gatk/). The detected variants are filtered and annotated with Cartagenia software and classified with Alamut Visual. It is not excluded that pathogenic mutations are being missed using this technology. At this moment, there is not enough information about the sensitivity of this technique with respect to the detection of deletions and duplications of more than 5 nucleotides and of somatic mosaic mutations (all types of sequence changes). HGNC approved Phenotype description including OMIM phenotype ID(s) OMIM median depth % covered % covered % covered gene symbol gene ID >10x >20x >30x A4GALT [Blood group, P1Pk system, P(2) phenotype], 111400 607922 101 100 100 99 [Blood group, P1Pk system, p phenotype], 111400 NOR polyagglutination syndrome, 111400 AAAS Achalasia‐addisonianism‐alacrimia syndrome, 231550 605378 73 100 100 100 AAGAB Keratoderma, palmoplantar,
    [Show full text]
  • The Genetic Mechanism That Links Hutchinson-Gilford Progeria Syndrome to Physiological Aging
    Department of Biosciences and Nutrition The genetic mechanism that links Hutchinson-Gilford progeria syndrome to physiological aging AKADEMISK AVHANDLING som för avläggande av medicine doktorsexamen vid Karolinska Institutet offentligen försvaras i Hörsalen, plan 4, Novum, Huddinge. Fredagen den 14 februari, 2014, kl 09.15 av Sofía Rodríguez Vásquez B.Sc. Licentiate in Biological Sciences Huvudhandledare: Fakultetsopponent: Docent Maria Eriksson Professor Karima Djabali Karolinska Institutet Technical University Munich Institutionen för Biovetenskaper och Department of Dermatology and Näringslära Institute for Medical Engineering Bihandledare: Betygsnämnd: Professor Karin Dahlman-Wright Docent Rickard Sandberg Karolinska Institutet Karolinska Institutet Institutionen för Biovetenskaper och Institutionen för Cell- och Molekylär Näringslära Biologi Professor Caroline Graff Professor Brun Ulfhake Karolinska Institutet Karolinska Institutet Institutionen för Neurobiologi, Institutionen för Neurovetenskap Vårdvetenskap och Samhälle Professor Jan Dumanski Uppsala Universitet Institutionen för Immunologi, Genetik och Patologi. Enheten för Medicinsk Genetik Stockholm 2014 DEPARTMENT OF BIOSCIENCES AND NUTRITION Karolinska Institutet, Stockholm, Sweden THE GENETIC MECHANISM THAT LINKS HUTCHINSON-GILFORD PROGERIA SYNDROME TO PHYSIOLOGICAL AGING Sofía Rodríguez Vásquez Stockholm 2014 All previously published papers were reproduced with permission from the publisher. Published by Karolinska Institutet. © Sofia Rodríguez Vásquez, 2014 ISBN 978-91-7549-372-5 Printed by Printed by 2014 Gårdsvägen 4, 169 70 Solna Dedicated to my beloved parents and life heroes: Benito Rodríguez Rodríguez & Doris Vásquez Silva ABSTRACT Aging is a complex process that is not completely understood. The study of segmental progeroid syndromes such as Hutchinson-Gilford progeria syndrome (HGPS) has allowed us to connect the common genetic mechanisms that occur in normal physiological aging, with the cellular alterations presented by this severe premature aging syndrome.
    [Show full text]
  • Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders
    Supplementary Online Content Lee H, Deignan JL, Dorrani N, Strom SP, Kantarci S, Quintero-Rivera F, et al. Clinical exome sequencing for genetic identification of rare Mendelian disorders. JAMA. doi:10.1001/jama.2014.14604. eMethods 1. Sample acquisition and pre-test sample processing eMethods 2. Exome capture and sequencing eMethods 3. Sequence data analysis eMethods 4. Variant filtration and interpretation eMethods 5. Determination of variant pathogenicity eFigure 1. UCLA Clinical Exome Sequencing (CES) workflow eFigure 2. Variant filtration workflow starting with ~21K variants across the exome and comparing the mean number of variants observed from trio-CES versus proband-CES eFigure 3. Variant classification workflow for the variants found within the primary genelist (PGL) eTable 1. Metrics used to determine the adequate quality of the sequencing test for each sample eTable 2. List of molecular diagnoses made eTable 3. List of copy number variants (CNVs) and uniparental disomy (UPD) reported and confirmatory status eTable 4. Demographic summary of 814 cases eTable 5. Molecular Diagnosis Rate of Phenotypic Subgroups by Age Group for Other Clinical Exome Sequencing References © 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 This supplementary material has been provided by the authors to give readers additional information about their work. © 2014 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/01/2021 eMethods 1. Sample acquisition and pre-test sample processing. Once determined by the ordering physician that the patient's presentation is clinically appropriate for CES, patients were offered the test after a counseling session ("pre-test counseling") [eFigure 1].
    [Show full text]
  • Blueprint Genetics Comprehensive Growth Disorders / Skeletal
    Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel Test code: MA4301 Is a 374 gene panel that includes assessment of non-coding variants. This panel covers the majority of the genes listed in the Nosology 2015 (PMID: 26394607) and all genes in our Malformation category that cause growth retardation, short stature or skeletal dysplasia and is therefore a powerful diagnostic tool. It is ideal for patients suspected to have a syndromic or an isolated growth disorder or a skeletal dysplasia. About Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders This panel covers a broad spectrum of diseases associated with growth retardation, short stature or skeletal dysplasia. Many of these conditions have overlapping features which can make clinical diagnosis a challenge. Genetic diagnostics is therefore the most efficient way to subtype the diseases and enable individualized treatment and management decisions. Moreover, detection of causative mutations establishes the mode of inheritance in the family which is essential for informed genetic counseling. For additional information regarding the conditions tested on this panel, please refer to the National Organization for Rare Disorders and / or GeneReviews. Availability 4 weeks Gene Set Description Genes in the Comprehensive Growth Disorders / Skeletal Dysplasias and Disorders Panel and their clinical significance Gene Associated phenotypes Inheritance ClinVar HGMD ACAN# Spondyloepimetaphyseal dysplasia, aggrecan type, AD/AR 20 56 Spondyloepiphyseal dysplasia, Kimberley
    [Show full text]
  • Prenatalscreen® Standard Technical Report
    About PrenatalScreen® Prenatal Test PrenatalScreen® Prenatal Test is a genetic test that analyses fetal DNA, obtained from CVS or amniotic fluid following an invasive prenatal diagnosis, to screen for monogenic disorders in the fetus. Using the latest technologies, including Next Generation Sequencing (NGS), PrenatalScreen® Prenatal Test screen 744 genes for mutations causing over 1.000 severe genetic disorders in the fetus. PrenatalScreen® Prenatal Test allows for a comprehensive care and enables patients to make more informed reproductive decisions. Offering PrenatalScreen® Prenatal Test to a patient during pregnancy allows her to gain more knowledge about the potential to pass along a condition to the fetus. Aim of the test PrenatalScreen® Prenatal Test analyses DNA extracted from fetal cells in the amniotic fluid, collected through amniocentesis, or in the chorionic villi through villocentesis (CVS). The aim of this diagnositc test is to assess severe genetic diseases in the fetus, including the most common diseases in the European population. Genes listed in Table 1 were selected according to the incidence in the population of the disease caused by mutations in such genes, the severity of the clinical phenotype at birth and the importance of the related pathogenetic picture, in accordance with the indications of the American College of Medical Genetics (ACMG)(Grody et al., Genet Med 2013:15:482–483). PrenatalScreen®: Indication for testing PrenatalScreen® Prenatal Test is intended for patients who meet any of the following criteria: • Personal/familial anamnesis of hereditary genetic diseases; • For expectant mothers wishing to reduce the risk of a genetic diseases in the fetus; • For natural or in vitro fertilization (IVF)-derived pregnancies: • For couples using heterologus IVF procedures (egg/sperm donors).
    [Show full text]
  • Blueprint Genetics Comprehensive Skeletal Dysplasias and Disorders
    Comprehensive Skeletal Dysplasias and Disorders Panel Test code: MA3301 Is a 251 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of disorders involving the skeletal system. About Comprehensive Skeletal Dysplasias and Disorders This panel covers a broad spectrum of skeletal disorders including common and rare skeletal dysplasias (eg. achondroplasia, COL2A1 related dysplasias, diastrophic dysplasia, various types of spondylo-metaphyseal dysplasias), various ciliopathies with skeletal involvement (eg. short rib-polydactylies, asphyxiating thoracic dysplasia dysplasias and Ellis-van Creveld syndrome), various subtypes of osteogenesis imperfecta, campomelic dysplasia, slender bone dysplasias, dysplasias with multiple joint dislocations, chondrodysplasia punctata group of disorders, neonatal osteosclerotic dysplasias, osteopetrosis and related disorders, abnormal mineralization group of disorders (eg hypopohosphatasia), osteolysis group of disorders, disorders with disorganized development of skeletal components, overgrowth syndromes with skeletal involvement, craniosynostosis syndromes, dysostoses with predominant craniofacial involvement, dysostoses with predominant vertebral involvement, patellar dysostoses, brachydactylies, some disorders with limb hypoplasia-reduction defects, ectrodactyly with and without other manifestations, polydactyly-syndactyly-triphalangism group of disorders, and disorders with defects in joint formation and synostoses. Availability 4 weeks Gene Set Description
    [Show full text]