DOCSLIB.ORG

Cohen Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cohen Syndrome Cohen syndrome Authors: Doctors Carlos García Ballesta1, Leonor Pérez Lajarín, Olga Cortés Lillo Creation date: November 2003 Update: October 2004 Scientific editor: Professor Didier Lacombe 1Hospital Morales Meseguer, University of Murcia, Avenida Marqués de los Vélez s/n 30.0008, Murcia, Spain. [email protected] Abstract Keywords Disease name and synonyms Definition Diagnostic criteria Differential diagnosis Etiology and pathogenesis Clinical manifestations Prevalence Course Treatment and therapeutic perspectives Preventive measures References Abstract In 1973, Cohen et al. described a new syndrome whose main features were obesity, hypotonia, mental retardation, characteristic craniofacial dysmorphism and abnormalities of the hands and feet. This syndrome is hereditary and transmitted as an autosomal recessive trait, with considerable variability of expression. The wide variety of manifestations observed, raises the possibility that not all of cases of Cohen syndrome correspond to the same process. It has been suggested that there are 2 types of Cohen syndrome, one with neutropenia and the other without neutropenia. Until now, nearly 100 cases have been reported. Orthodontic and orthopedic management as well as psychopedagogic measures and possible growth hormone therapy are necessary. Obesity progresses over time, along with the orthopedic alterations and oral problems, though the patient life expectancy is not altered in any significant way. Recently, characterization of a novel gene, COH1 (locus 8q22-q23) that is mutated in patients with Cohen syndrome has been reported. COH1 encodes a putative transmembrane protein which may be is involved in vesicle-mediated sorting and transport of proteins within the cell. Keywords Cohen syndrome, obesity, mental retardation, craniofacial dysmorphism, COH1 gene. Disease name and synonyms Hypotonia, obesity, and prominent incisors. Diagnostic criteria Pepper syndrome Diagnosis is based on clinical examination. CHS1, formerly However, in Cohen syndrome, the phenotype with strict clinical criteria is extremely difficult to Definition establish. This is because a wide variety of In 1973, Cohen et al. described a new syndrome manifestations are observed, raising the whose main features were obesity, hypotonia, possibility that not all of them correspond to the mental retardation, characteristic craniofacial same process. It has been suggested that there dysmorphism and abnormalities of the hands are 2 types of Cohen syndrome, one with and feet. This syndrome is hereditary and neutropenia and the other without neutropenia transmitted as an autosomal recessive trait, with (Norio, 1994). Therefore, in young persons with considerable variability of expression. hypotonia and motor-development retardation, hematological screening for García Ballesta C., Pérez Lajarín L., Cortés Lillo O. Cohen syndrome. Orphanet encyclopedia October 2004: http://www.orpha.net/data/patho/GB/uk-cohen.pdf 1 leukemia/neutropenia should be a routine - congenital obesity syndromes, particularly the procedure, because these defects are present Prader-Willi (Laurence et al., 1981) and Bardet- from birth (Fryns et al. 1996). Biedl syndrome (Smith , 1976); Neutropenia in Cohen syndrome is congenital, - Marfan syndrome, Sotos syndrome, chronic, intermittent but not fatal . Possible hypothyroidism, minimal brain dysfunction and compensatory defense mechanisms are not most frequetly mental retardation of unknown known but patients with Cohen syndrome seem causes are the diagnosis most frequently evoked to be able to respond to severe bacterial before the diagnosis of cohen syndrome is infections by granulocytosis (Alaluusua et al. formely established; 1997) - other syndromes must be differentiated such as The global clinical manifestations, may be Urban Rogers Meyers syndrome (Urban et al., sufficiently characteristic – though due 1976), and Vásquez syndrome (Vasquez et al. evaluation is required for the cardiac alterations 1979). (based on echocardiography) and ophthalmological disorders. Etiology and pathogenesis A specific clinical phenotype has been Transmission is autosomal recessive (locus delineated in a homogeneous cohort of Finnish 8q22-q23) and both sexes are equally affected. patients with Cohen syndrome (Kivitie-Kallio et The pathogenic mechanism of Cohen syndrome al., 2001). The clinical picture is as follows: is unknown. However involvement of the - non progressive psychomotor retardation ; connective tissue, muscle, brain, retina, and - motor clumsiness; occasionally the hematopoietic system (Norio et - microcephaly; al., 1984) suggests that a possible metabolic - typical facial features (high-arched or wave- alteration or an alteration to the connective shaped eyelids, a short philtrum, thick hair, low tissue itself could be the origin of the problem, as hairline); previously proposed by Friedman and Sack. - childhood hypotonia and hyperextensibility of The genetic abnormality would induce a the joints; connective tissue alteration, accounting for the - progressive retinochoroidal dystrophy; joint hyperlaxity observed, possible mitral valve - myopia; prolapse and frequent orthopedic alterations. - intermittent isolated neutropenia, Cases have been reported in siblings, granulocytopenia. sometimes with consanguineous parents (Arcas In the non-Finnish patients suspected with et al., 1991), and one case of transmission with Cohen syndrome, confusing phenotypic an autosomal dominant mode has also been variability prevails (Chandler et al. 2003). published (Mejia-Baltodano et al., 1997) . Obesity, although frequently mentioned as a Tahvanainen et al. and Hilton et al. identified the characteristic finding, is not relevant. locus of Cohen syndrome on chromosome 8q22- Retinochoroidal dystrophy or intermittent q23. neutropenia in reports of some patients has not Recently, Kolehmainen et al. reported the been confirmed. Thus, a distinct clinical (and characterization of a novel gene, COH1, that is possibly also genetic) heterogeneity prevails mutated in patients with Cohen syndrome. The among reported patients with Cohen syndrome. longest transcript is widely expressed and is Recently, a comprehensive genotype-phenotype transcribed from 62 exons that span a genomic study on the largest cohort of patients with region of approximately 864 kb. COH1 encodes Cohen syndrome assembled to date has been a putative transmembrane protein of 4,022 published (Kolehmainen et al., 2004). Twenty- amino acids, with a complex domain structure. two different COH1 mutations have been found, Homology to the Saccharomyces cerevisiae By contrast, no COH1 mutations were found in VPS13 protein suggests a role for COH1 in patients with a provisional diagnosis of Cohen vesicle-mediated sorting and transport of syndrome who did not fulfil the diagnostic criteria proteins within the cell. ("Cohen-like" syndrome). This study provides a molecular confirmation of the clinical phenotype Clinical manifestations associated with Cohen syndrome and provides a Compilation of all reported clinical manifestations basis for laboratory screening that will be in Cohen syndrome allows the listing of those valuable in its diagnosis. features occurring in 75-100% of all cases. These manifestations affect general appearance, Differential diagnosis head, chest, genital organs, limbs, spine and The differential diagnosis is to be established nervous system (see Table 1). with: The least common features (occurring in less than 25% of all cases) are: microphthalmia, García Ballesta C., Pérez Lajarín L., Cortés Lillo O. Cohen syndrome. Orphanet encyclopedia October 2004: http://www.orpha.net/data/patho/GB/uk-cohen.pdf 2 coloboma, mottled retinal pigment, , and syndactyly, less frequent dislocated hip. (Friedman et al. 1982). hip luxation, increased 53% In recent publication (Garcia Ballesta et al., frequency of rheumatoid 2003), our team presents study, which details 2 arthritis new patients, 2 brothers (8 and 11 years old), Spine Scoliosis or lordosis 50% and mainly analyses dentomaxillary anomalies Occult spina bifida Rarely that until now have not been studied in depth. In In addition to mental this study, the mandible, characterized as Nervous retardation and hypotonia, hypoplastic in Cohen syndrome, appears to be in system other possible though non- a normal position; what really exists is a habitual features are maxillary hyperplasia of genetic origin. We also seizures and deafness put forward an observation hitherto undescribed in the literature: dental agenesis. Table 1: Features in Cohen syndrome Reduced intrauterine 82% By means of an analysis, similar to those of growth (though not Steiner and Rickets, we have obtained values particularly important) that make us think that mandibular hypoplasia is Apparent diminished not present but that, on the contrary, the mental status attributable to 82% mandibula is in a normal position and that there General the observed fascies, with is present, genetically, maxillary hyperplasia and appearance mental retardation consequently labial incompetence (Garcia Obesity, more manifest 90% Ballesta et al., 2003). The term "prominent towards 5-6 years of age, incisors", which constantly appears in the in contrast with fine hands literature, is no more than the consequence of Micrognathia 100% maxillary prognathia and labial interposition. Microcephaly 50% Short philtrum 90% Prevalence High nasal bridge 65% Since the first description of Cohen syndrome, Malar and upper maxillary 82% nearly 100 cases have been reported, the
Load more

Recommended publications
  • My Beloved Neutrophil Dr Boxer 2014 Neutropenia Family Conference
    The Beloved Neutrophil: Its Function in Health and Disease Stem Cell Multipotent Progenitor Myeloid Lymphoid CMP IL-3, SCF, GM-CSF CLP Committed Progenitor MEP GMP GM-CSF, IL-3, SCF EPO TPO G-CSF M-CSF IL-5 IL-3 SCF RBC Platelet Neutrophil Monocyte/ Basophil B-cells Macrophage Eosinophil T-Cells Mast cell NK cells Mature Cell Dendritic cells PRODUCTION AND KINETICS OF NEUTROPHILS CELLS % CELLS TIME Bone Marrow: Myeloblast 1 7 - 9 Mitotic Promyelocyte 4 Days Myelocyte 16 Maturation/ Metamyelocyte 22 3 – 7 Storage Band 30 Days Seg 21 Vascular: Peripheral Blood Seg 2 6 – 12 hours 3 Marginating Pool Apoptosis and ? Tissue clearance by 0 – 3 macrophages days PHAGOCYTOSIS 1. Mobilization 2. Chemotaxis 3. Recognition (Opsonization) 4. Ingestion 5. Degranulation 6. Peroxidation 7. Killing and Digestion 8. Net formation Adhesion: β 2 Integrins ▪ Heterodimer of a and b chain ▪ Tight adhesion, migration, ingestion, co- stimulation of other PMN responses LFA-1 Mac-1 (CR3) p150,95 a2b2 a CD11a CD11b CD11c CD11d b CD18 CD18 CD18 CD18 Cells All PMN, Dendritic Mac, mono, leukocytes mono/mac, PMN, T cell LGL Ligands ICAMs ICAM-1 C3bi, ICAM-3, C3bi other other Fibrinogen other GRANULOCYTE CHEMOATTRACTANTS Chemoattractants Source Activators Lipids PAF Neutrophils C5a, LPS, FMLP Endothelium LTB4 Neutrophils FMLP, C5a, LPS Chemokines (a) IL-8 Monocytes, endothelium LPS, IL-1, TNF, IL-3 other cells Gro a, b, g Monocytes, endothelium IL-1, TNF other cells NAP-2 Activated platelets Platelet activation Others FMLP Bacteria C5a Activation of complement Other Important Receptors on PMNs ñ Pattern recognition receptors – Detect microbes - Toll receptor family - Mannose receptor - bGlucan receptor – fungal cell walls ñ Cytokine receptors – enhance PMN function - G-CSF, GM-CSF - TNF Receptor ñ Opsonin receptors – trigger phagocytosis - FcgRI, II, III - Complement receptors – ñ Mac1/CR3 (CD11b/CD18) – C3bi ñ CR-1 – C3b, C4b, C3bi, C1q, Mannose binding protein From JG Hirsch, J Exp Med 116:827, 1962, with permission.
    [Show full text]
  • Blueprint Genetics Bone Marrow Failure Syndrome Panel
    Bone Marrow Failure Syndrome Panel Test code: HE0801 Is a 135 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of inherited bone marrow failure syndromes. The genes on this panel are included in the Comprehensive Hematology Panel. About Bone Marrow Failure Syndrome Inherited bone marrow failure syndromes (IBMFS) are a diverse set of genetic disorders characterized by the inability of the bone marrow to produce sufficient circulating blood cells. Bone marrow failure can affect all blood cell lineages causing clinical symptoms similar to aplastic anemia, or be restricted to one or two blood cell lineages. The clinical presentation may include thrombocytopenia or neutropenia. Hematological manifestations may be accompanied by physical features such as short stature and abnormal skin pigmentation in Fanconi anemia and dystrophic nails, lacy reticular pigmentation and oral leukoplakia in dyskeratosis congenita. Patients with IBMFS have an increased risk of developing cancer—either hematological or solid tumors. Early and correct disease recognition is important for management and surveillance of the diseases. Currently, accurate genetic diagnosis is essential to confirm the clinical diagnosis. The most common phenotypes that are covered by the panel are Fanconi anemia, Diamond-Blackfan anemia, dyskeratosis congenita, Shwachman-Diamond syndrome and WAS-related disorders. Availability 4 weeks Gene Set Description Genes in the Bone Marrow Failure Syndrome Panel and their clinical significance
    [Show full text]
  • Approach to the Genetic Diagnosis of Autism Why Genetics? Why
    11/2/2013 Approach to the Genetic Diagnosis of Autism Margaret Rieley, MD November 2, 2013 Why Genetics? 1:2500 (1980s) 1:88 to 1:100 (current) >500% increase over the last 20 years Declared “epidemic” 4-5 times more prevalent in boys Present in all racial, ethnic, social groups High heritability MZ twins 60-90% concordance DZ twins 0-10% concordance Why Genetics? Examine and evaluate patient and family members Determine etiology Definitive diagnosis helps patient acquire services Provide information on prognosis Screen and potentially prevent morbidity Counsel on recurrence risk Targeted therapies (metabolic disorders, FXS) Empower the family by knowledge of underlying cause 1 11/2/2013 Evaluation Scheme (ACMG) Pre-evaluation ◦ Accurate ASD diagnosis ◦ Sensory screening: complete audiogram ◦ Cognitive testing ◦ EEG (if seizures suspected) ◦ Verify newborn screening results ◦ Prenatal history (GA, Wt, parental ages, exposures) ◦ Karyotype ◦ Fragile X (AAP recommendations) Tier 1 - Physical Exam Evaluation for known syndromes or associated conditions Intellectual disability (ID) (75%) Dysmorphic features and epilepsy (25%) MRI and EEG abnormalities (less common) Microceppyhaly (()10%) Macrocephaly (20–40%) Congenital anomaly (6% vs. 3% in gen pop) ◦ Congenital anomalies double risk of autism (0.4% vs. 0.2% in gen pop) ◦ Brain and eye more likely to be associated with autism Majority are nondysmorphic with no other medical features suggestive of a syndrome 1st Tier, continued Woods lamp exam Targeted testing if specific diagnosis is considered ◦ Rubella titers Rare (<10 cases/yr) Sensorineural deafness (58%) Eye abnormalities—retinopathy, cataract and microphthalmia (43%) Congenital heart disease (50%) ◦ “Standard” metabolic screening clinical indicators present suspected condition not screened for on NB screening ◦ Urine mucopolysaccharides and organic acids ◦ Serum lacate, amino acids, ammonia, acyl-carnitine profile, CK, LFTs.
    [Show full text]
  • Mutations in ELANE and COH1 (VPS13B) Genes Cause Severe
    C al & ellu ic la n r li Im C m f u Journal of o n l o a l n o r g u y o J Beene et al., J Clin Cell Immunol 2015, 6:6 ISSN: 2155-9899 Clinical & Cellular Immunology DOI: 10.4172/2155-9899.1000378 Case Report Open Access Mutations in ELANE and COH1 (VPS13B) Genes Cause Severe Neutropenia in a Patient with Cohen Syndrome Lauren Beene1,2, Baozhong Xin1, Claudia Lukas3 and Heng Wang1,2* 1DDC Clinic -- Center for Special Needs Children, Middlefield, Ohio, USA 2Department of Pediatrics, Case Western Reserve University School of Medicine, Rainbow Babies and Children’s Hospital, Cleveland, Ohio, USA 3Department of Hematology-Oncology, All Children’s Hospital, St. Petersburg, Florida, USA *Corresponding author: Heng Wang, MD, PhD, DDC Clinic -- Center for Special Needs Children, 14567 Madison Road, Middlefield, OH 44062, USA, Tel: 440-632-1668; Fax: 440-632-1697; E-mail: [email protected] Received date: October 27, 2015; Accepted date: December 16, 2015; Published date: December 28, 2015 Copyright: © 2015 Beene L, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract In this case report we describe a patient with cohen syndrome and severe neutropenia. The patient was found to have a mutation of previously undetermined significance in the ELANE gene and compound heterozygous mutations in the COH1 gene causing Cohen syndrome. While the mutation in ELANE may not have led to clinically significant neutropenia independently, the presence of this mutation in conjunction with mutations in COH1 led to neutropenia that was more severe than what is typically seen in Cohen syndrome.
    [Show full text]
  • ESID Registry – Working Definitions for Clinical Diagnosis of PID
    ESID Registry – Working Definitions for Clinical Diagnosis of PID These criteria are only for patients with no genetic diagnosis*. *Exceptions: Atypical SCID, DiGeorge syndrome – a known genetic defect and confirmation of criteria is mandatory Available entries (Please click on an entry to see the criteria.) Page Acquired angioedema .................................................................................................................................................................. 4 Agammaglobulinaemia ................................................................................................................................................................ 4 Asplenia syndrome (Ivemark syndrome) ................................................................................................................................... 4 Ataxia telangiectasia (ATM) ......................................................................................................................................................... 4 Atypical Severe Combined Immunodeficiency (Atypical SCID) ............................................................................................... 5 Autoimmune lymphoproliferative syndrome (ALPS) ................................................................................................................ 5 APECED / APS1 with CMC - Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) .................. 5 Barth syndrome ...........................................................................................................................................................................
    [Show full text]
  • The Open Neurology Journal, 2016, 10, I-Xv I the Open Neurology Journal Supplementary Material Content List Available At
    Send Orders for Reprints to [email protected] The Open Neurology Journal, 2016, 10, i-xv i The Open Neurology Journal Supplementary Material Content list available at: www.benthamopen.com/TONEUJ/ DOI: 10.2174/1874205X01610010143 Functional and Genomic Features of Human Genes Mutated in Neuropsychiatric Disorders Diego A. Forero1,4, *, Carlos F. Prada2 and George Perry3 1Laboratory of NeuroPsychiatric Genetics, Biomedical Sciences Research Group, School of Medicine, Universidad Antonio Nariño. Bogotá, Colombia 2Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Universidad del Tolima. Ibagué, Colombia 3College of Sciences, University of Texas at San Antonio, San Antonio, Texas, USA Table S1. List of genes known to harbor mutations for NPD. GENE SYMBOL GENE NAME ENSEMBL ID DISORDERS PMID ATP-BINDING CASSETTE, SUB- ABCB7 FAMILY B (MDR/TAP), MEMBER 7 ENSG00000131269 X-linked sideroblastic anemia and ataxia 10196363 ATP-BINDING CASSETTE, SUB- ABCD1 FAMILY D (ALD), MEMBER 1 ENSG00000101986 X-linked adrenoleukodystrophy 8441467 ABHYDROLASE DOMAIN ABHD12 CONTAINING 12 ENSG00000100997 Polyneuropathy, hearing loss and ataxia 20797687 ACYL-COA SYNTHETASE LONG- ACSL4 CHAIN FAMILY MEMBER 4 ENSG00000068366 nonspecific X-linked mental retardation 11889465 activity-dependent neuroprotector ADNP homeobox ENSG00000101126 autism spectrum disorder and intellectual disability 24531329 AGTR2 ANGIOTENSIN II RECEPTOR, TYPE 2 ENSG00000180772 X-linked mental retardation 12089445 ABELSON HELPER INTEGRATION AHI1 SITE 1 ENSG00000135541 Joubert
    [Show full text]
  • Cohen Syndrome
    Cohen syndrome What is Cohen syndrome? Cohen syndrome is an inherited disease with variable signs and symptoms. Cohen syndrome is known to be caused by mutations in the gene that produces the VPS13B protein; however, the function of the VPS13B protein is currently unknown.1 What are the symptoms of Cohen syndrome and what treatment is available? The symptoms of Cohen syndrome are variable and may include1.2: • Developmental delay • Intellectual disability • Microcephaly (small head) • Hypotonia (poor muscle tone) • Nearsightedness • Retinal dystrophy (degeneration of the retina of the eye) • Joint hypermobility (large range of movement) • Neutropenia (abnormal white blood cell count) • Overly friendly behavior • Truncal obesity • Narrow hands and feet • Delayed puberty • Distinctive facial features Treatment is supportive and focuses on prevention of complications and management of symptoms.2 How is Cohen syndrome inherited? Cohen syndrome is an autosomal recessive disease caused by mutations in the VPS13B gene.1 An individual who inherits one copy of a VPS13B gene mutation is a carrier. Carriers are not affected with Cohen syndrome. An individual who inherits two VPS13B mutations, one from each parent, is expected to be affected with Cohen syndrome. If both members of a couple are carriers of mutations in the same gene, the risk for an affected child is 25% in each pregnancy; therefore, it is especially important that the reproductive partner of a carrier be offered testing. Who is at risk for Cohen syndrome? Cohen syndrome is a rare condition with an unknown prevalence. It may be seen more commonly among the Finnish population.3 Having a relative who is a carrier or who is affected can increase an individual’s risk to be a carrier.
    [Show full text]
  • The Myriad Foresight® Carrier Screen
    The Myriad Foresight® Carrier Screen 180 Kimball Way | South San Francisco, CA 94080 www.myriadwomenshealth.com | [email protected] | (888) 268-6795 The Myriad Foresight® Carrier Screen - Disease Reference Book 11-beta-hydroxylase-deficient Congenital Adrenal Hyperplasia ...............................................................................................................................................................................8 6-pyruvoyl-tetrahydropterin Synthase Deficiency....................................................................................................................................................................................................10 ABCC8-related Familial Hyperinsulinism..................................................................................................................................................................................................................12 Adenosine Deaminase Deficiency ............................................................................................................................................................................................................................14 Alpha Thalassemia ....................................................................................................................................................................................................................................................16 Alpha-mannosidosis ..................................................................................................................................................................................................................................................18
    [Show full text]
  • Genetic Testing Medical Policy – Genetics
    Genetic Testing Medical Policy – Genetics Please complete all appropriate questions fully. Suggested medical record documentation: • Current History & Physical • Progress Notes • Family Genetic History • Genetic Counseling Evaluation *Failure to include suggested medical record documentation may result in delay or possible denial of request. PATIENT INFORMATION Name: Member ID: Group ID: PROCEDURE INFORMATION Genetic Counseling performed: c Yes c No **Please check the requested analyte(s), identify number of units requested, and provide indication/rationale for testing. 81400 Molecular Pathology Level 1 Units _____ c ACADM (acyl-CoA dehydrogenase, C-4 to C-12 straight chain, MCAD) (e.g., medium chain acyl dehydrogenase deficiency), K304E variant _____ c ACE (angiotensin converting enzyme) (e.g., hereditary blood pressure regulation), insertion/deletion variant _____ c AGTR1 (angiotensin II receptor, type 1) (e.g., essential hypertension), 1166A>C variant _____ c BCKDHA (branched chain keto acid dehydrogenase E1, alpha polypeptide) (e.g., maple syrup urine disease, type 1A), Y438N variant _____ c CCR5 (chemokine C-C motif receptor 5) (e.g., HIV resistance), 32-bp deletion mutation/794 825del32 deletion _____ c CLRN1 (clarin 1) (e.g., Usher syndrome, type 3), N48K variant _____ c DPYD (dihydropyrimidine dehydrogenase) (e.g., 5-fluorouracil/5-FU and capecitabine drug metabolism), IVS14+1G>A variant _____ c F13B (coagulation factor XIII, B polypeptide) (e.g., hereditary hypercoagulability), V34L variant _____ c F2 (coagulation factor 2) (e.g.,
    [Show full text]
  • Inherited Neutropenia Gene Sequencing Panel
    Inherited Neutropenia Gene Sequencing Panel Genes Tested: against overwhelming bacterial infection. Nonsense and frameshift variants affecting the carboxyl terminus are AK2 AP3B1 CD40LG CLPB quite common, while missense variants are seen more CSF3R CXCR2 CXCR4 DNAJC21 commonly in cyclic neutropenia patients. However, there EFL1 EIF2AK3 ELANE G6PC3 is considerable overlap of genotype with phenotype, GATA1 GATA2 GFI1 HAX1 even within families. Mutations in GFI1, HAX1, G6PC3, VPS45 and CFS3R are much less frequent causes of HYOU1 JAGN1 LAMTOR2 LYST severe congenital neutropenia. Variants within the Cdc42 MRTFA RAB27A RAC2 RMRP binding site of WAS are also associated with an X-linked (MKL1) form of congenital neutropenia. RUNX1 SBDS SLC37A4 SMARCD2 The diagnostic criteria for SCN include: SRP54 STK4 TAZ TCIRG1 TCN2 TP53 USB1 VPS13B • Early childhood onset of profound neutropenia (<0.5 × 109/L) VPS45 WAS WDR1 WIPF1 • Recurrent life-threatening bacterial infections • Promyelocytic maturation arrest in the bone marrow Description: This panel detects the most common genetic causes Syndromic neutropenia: Significant neutropenia is a of severe congenital neutropenia as well as genetic common feature of several genetic syndromes associated syndromes often associated with neutropenia, with extra-hematopoietic abnormalities including Barth including Barth syndrome, Chediak-Higashi syndrome, syndrome, Cohen syndrome secondary to VPS13B variants, Clericuzio-type poikiloderma with neutropenia, Cohen Chediak-Higashi syndrome, Clericuzio-type poikiloderma syndrome, GATA1-related X linked cytopenia, GATA2 with neutropenia, GATA1-related X linked cytopenia, deficiency, glycogen storage disease type 1B, Griscelli GATA2 deficiency, glycogen storage disease type 1B, syndrome type 2, Hermansky-Pudlak syndrome type Griscelli syndrome type 2, Hermansky-Pudlak syndrome 2, p14 deficiency, Shwachman-Diamond syndrome, type 2, p14 deficiency, Shwachman-Diamond syndrome and WHIM syndrome, and Wiscott-Aldrich syndrome.
    [Show full text]
  • Golgipathies in Neurodevelopment: a New View of Old Defects Sowmyalakshmi Rasika, Sandrine Passemard, Alain Verloes, Pierre Gressens, Vincent El Ghouzzi
    Golgipathies in Neurodevelopment: A New View of Old Defects Sowmyalakshmi Rasika, Sandrine Passemard, Alain Verloes, Pierre Gressens, Vincent El ghouzzi To cite this version: Sowmyalakshmi Rasika, Sandrine Passemard, Alain Verloes, Pierre Gressens, Vincent El ghouzzi. Golgipathies in Neurodevelopment: A New View of Old Defects. Developmental Neuroscience, Karger, 2019, 40 (5-6), pp.396-416. 10.1159/000497035. hal-02322665 HAL Id: hal-02322665 https://hal.archives-ouvertes.fr/hal-02322665 Submitted on 2 Jun 2020 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Rasika et al, Golgipathies and Neurodevelopment 1 2 Golgipathies in Neurodevelopment: 3 A New View of Old Defects 4 5 1,2 1,2 1,2 6 Sowmyalakshmi Rasika , Sandrine Passemard , Alain Verloes , Pierre 1,3 1* 7 Gressens , Vincent El Ghouzzi 8 9 1. PROTECT, INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France 10 2. AP HP, Hôpital Robert Debré, UF de Génétique Clinique, Paris, France 11 3. Centre for the Developing Brain, Division of Imaging Sciences and Biomedical 12 Engineering, King’s College London, King’s Health Partners, St. Thomas’ Hospital, 13 London, United Kingdom 14 15 *Corresponding author: 16 Vincent El Ghouzzi 17 Address: Inserm U1141, Hôpital Robert-Debré, 48 Boulevard Sérurier, F-75019, 18 Paris, France.
    [Show full text]
  • NHS Grampian Medical Genetics GEN FORM 215
    NHS Grampian Medical Genetics GEN FORM 215 NHS GRAMPIAN GENETICS & MOLECULAR PATHOLOGY LABORATORY SERVICES REQUEST FOR PRIMARY IMMUNODEFICIENCY & PAEDIATRIC RHEUMATOLOGY TESTING North East Scotland Genetics Service, NHS Grampian, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD. www.nhsgrampian.org/medicalgenetics Tel: 01224 553893 / 553820 Email: [email protected] Essential Patient Demographics (Patient label can be used) Forename: Surname: CHI No.: Date of Birth: Male / Female (Circle as appropriate) Address (must include postcode): Postcode: Pedigree No. (if known): Genetics Reference No. (if known): Essential Referrer Details Referring Clinician(s): Address for Report: Copy to: Ward / Department / Practice: Email address: Telephone no.: Essential Sample Information Sample Type: Date Taken: Time Taken: Urgent analysis required: YES / NO DNA / Molecular Genetics only High Risk: YES / NO Storage only: YES / NO If yes, please state risk ______________ Notify lab in advance if high risk Specific test requested – clear indication of appropriate test is required SPIDeR SCREEN: SINGLE GENE SCREEN: see page 5 for PREDICTIVE TEST: please enter Please tick relevant boxes on pages 2-5. details proband’s and genetic variant details PID classification according to IUIS 2017 (J Clin Immunol., 2018 38:129– 143) Reason for referral & relevant clinical information: CONSENT: It is the responsibility of the referring clinician to obtain informed consent from the patient / carer for the test and for the sample to be stored for future diagnostic testing. Signature of referring clinician: __________________________________ Print name: _________________________________ GEN FORM 215 Primary Immunodeficiency Request Form for Genetic Testing Version 1.4 (03/2021) Page 1 of 5 NHS Grampian Medical Genetics GEN FORM 215 I.
    [Show full text]