Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency

Autor: Alice Masurel, Yannis Duffourd, Bénédicte Gérard, Christiane Zweier, Thomas Arnesen, Bernt Popp, Melissa P. Wasserstein, Cyril Mignot, Nicholas AhMew, Laetitia Lampert, Boris Keren, Jean Baptiste Rivière, Caroline Nava, Laurence Faivre, Chloé Saunier, Marjon van Slegtenhorst, Paul Kuentz, Christel Thauvin-Robinet, Marina Blenski, Svein Isungset Støve, Paula Goldenberg, Amélie Piton, André Reis, Julien Thevenon, Frédéric Huet, Ange Line Bruel, Grazia M.S. Mancini, Kamer Tezcan, Charlotte de Bie, Bruno Leheup, Bertrand Isidor
Přispěvatelé: Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de pédiatrie (CHU de Dijon), Department of Molecular Biology, University of Bergen ( UIB ), Dpt of Surgery [Bergen], Haukeland University Hospital, Friedrich-Alexander Universität Erlangen-Nürnberg ( FAU ), Laboratoire de Génétique Moléculaire [CHRU Strasbourg], CHRU Strasbourg, Division of Genetics & Metabolism, Children's National Medical Center, Dpt of Genetics [Utrecht], UMC Utrecht, Massachusetts General Hospital [Boston] ( MGH ), Service de génétique médicale - Unité de génétique clinique [Nantes], Université de Nantes ( UN ) -Centre hospitalier universitaire de Nantes ( CHU Nantes ), Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Service de Génétique Médicale [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Nutrition-Génétique et Exposition aux Risques Environnementaux ( NGERE ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Lorraine ( UL ), Centre de Référence des Déficiences Intellectuelles de Causes Rares, Kaiser Permanente, ErasmusMC University Medical Center Rotterdam, Dpts of Genetics and Genomic Sciences and Pediatrics [New York], Icahn School of Medicine at Mount Sinai [New York], Université de Bourgogne ( UB ), Génétique des Anomalies du Développement ( GAD ), Université de Bourgogne ( UB ) -IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire de Génétique Moléculaire, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), University of Bergen (UiB), University of Bergen (UiB)-University of Bergen (UiB), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University Medical Center [Utrecht], Massachusetts General Hospital [Boston], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Université de Bourgogne (UB), Génétique des Anomalies du Développement (GAD), Université de Bourgogne (UB)-IFR100 - Structure fédérative de recherche Santé-STIC, Laboratoire de génétique moléculaire (hôpital général, CHU Dijon), Hôpital général (CHU Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), IFR100 - Structure fédérative de recherche Santé-STIC-Université de Bourgogne (UB), Clinical Genetics
Rok vydání: 2016
Předmět:
0301 basic medicine
Male
Models
Molecular
Microcephaly
Mutation
Missense
Biology
Germline
KEY WORDS: NAA10
03 medical and health sciences
Germline mutation
Genes
X-Linked
Intellectual disability
Genetics
medicine
Missense mutation
Humans
Genetic Predisposition to Disease
N-Terminal Acetyltransferase E
Genetics (clinical)
Genetic Association Studies
Germ-Line Mutation
N-Terminal Acetyltransferase A
Research Articles
X-linked
[SDV.GEN]Life Sciences [q-bio]/Genetics
Regional Council of Burgundy
Mosaicism
N-terminal acetylation
Acetylation
medicine.disease
Phenotype
Pedigree
Ogden Syndrome
X‐linked
030104 developmental biology
NAA10
intellectual disability
N‐terminal acetylation
Contract grant sponsors: Dijon University Hospital
Female
[ SDV.GEN ] Life Sciences [q-bio]/Genetics
NAA15
Research Article
Zdroj: Human Mutation
Human Mutation, Wiley, 2016, 〈10.1002/humu.23001〉
Human Mutation, 2016, ⟨10.1002/humu.23001⟩
Human Mutation, Wiley, 2016, ⟨10.1002/humu.23001⟩
Human Mutation, 37(8), 755-764. Wiley-Liss Inc.
ISSN: 1059-7794
1098-1004
Popis: International audience; N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ line mosaicism in another girl and her more severely affected and deceased brother. In vitro enzymatic assays for the novel, recurrent mutations p.(Arg83Cys) and p.(Phe128Leu) revealed reduced catalytic activity. X-inactivation was random in five females. The core phenotype of X-linked NAA10-related N-terminal-acetyltransferase deficiency in both males and females includes developmental delay, severe intellectual disability, postnatal growth failure with severe microcephaly, and skeletal or cardiac anomalies. Genotype–phenotype correlations within and between both genders are complex and may include various factors such as location and nature of mutations, enzymatic stability and activity, and X-inactivation in females.
Databáze: OpenAIRE
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