دورية أكاديمية
De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability.
| العنوان: | De novo coding variants in the AGO1 gene cause a neurodevelopmental disorder with intellectual disability. |
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| المؤلفون: | Schalk A; Institut de génétique médicale d'Alsace (IGMA), Laboratoire de Diagnostic Génétique, Hôpitaux universitaires de Strasbourg, Strasbourg, Alsace, France., Cousin MA; Department of Quantitative Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA., Dsouza NR; Bioinformatics Research and Development Laboratory, Genomics Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Challman TD; Autism & Developmental Medicine Institute, Geisinger-Lewistown Hospital, Lewistown, Pennsylvania, USA., Wain KE; Autism & Developmental Medicine Institute, Geisinger-Lewistown Hospital, Lewistown, Pennsylvania, USA., Powis Z; Department of Clinical Genomics, Ambry Genetics Corp, Aliso Viejo, California, USA., Minks K; Department of Clinical Genomics, Ambry Genetics Corp, Aliso Viejo, California, USA., Trimouille A; Service de Génétique Médicale, Centre de Référence Anomalies du Développement et Syndrome Malformatifs, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France.; Maladies rares: Génétique et Métabolisme (MRGM), INSERM U1211, Université de Bordeaux Centre de Génomique Fonctionnelle de Bordeaux, Bordeaux, Nouvelle-Aquitaine, France., Lasseaux E; Service de Génétique Médicale, Centre de Référence Anomalies du Développement et Syndrome Malformatifs, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France., Lacombe D; Service de Génétique Médicale, Centre de Référence Anomalies du Développement et Syndrome Malformatifs, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France.; Maladies rares: Génétique et Métabolisme (MRGM), INSERM U1211, Université de Bordeaux Centre de Génomique Fonctionnelle de Bordeaux, Bordeaux, Nouvelle-Aquitaine, France., Angelini C; Service de Génétique Médicale, Centre de Référence Anomalies du Développement et Syndrome Malformatifs, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France.; Maladies rares: Génétique et Métabolisme (MRGM), INSERM U1211, Université de Bordeaux Centre de Génomique Fonctionnelle de Bordeaux, Bordeaux, Nouvelle-Aquitaine, France., Michaud V; Service de Génétique Médicale, Centre de Référence Anomalies du Développement et Syndrome Malformatifs, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France.; Maladies rares: Génétique et Métabolisme (MRGM), INSERM U1211, Université de Bordeaux Centre de Génomique Fonctionnelle de Bordeaux, Bordeaux, Nouvelle-Aquitaine, France., Van-Gils J; Département de Génétique Médicale, Centre de Référence Anomalies du Développement et Syndrome Malformatifs, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, Aquitaine, France., Spataro N; Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí, Sabadell, Catalunya, Spain., Ruiz A; Genetics Laboratory, UDIAT-Centre Diagnòstic, Parc Taulí Hospital Universitari, Institut d'Investigació i Innovació Parc Taulí, Sabadell, Catalunya, Spain., Gabau E; Paediatric Unit, Parc Tauli Foundation-UAB University Institute, Sabadell, Catalunya, Spain., Stolerman E; 106 Gregor Mendel Cir, Greenwood Genetic Center Inc, Greenwood, South Carolina, USA., Washington C; 106 Gregor Mendel Cir, Greenwood Genetic Center Inc, Greenwood, South Carolina, USA., Louie R; 106 Gregor Mendel Cir, Greenwood Genetic Center Inc, Greenwood, South Carolina, USA., Lanpher BC; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA., Kemppainen JL; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA., Innes M; Department of Medical Genetics and Alberta Children's Hospital Research Institute, University of Calgary Cumming School of Medicine, Calgary, Alberta, Canada., Kooy F; Center Medical Genetics, University Hospital Antwerp, Antwerp, Belgium., Meuwissen M; Center Medical Genetics, University Hospital Antwerp, Antwerp, Belgium., Goldenberg A; Normandie Univ, UNIROUEN, Inserm U1245 and Rouen University Hospital, Department of Genetics and Reference Center for Developmental Disorders, Centre Hospitalier Universitaire de Rouen, Rouen, Normandie, France., Lecoquierre F; 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Division of Medical Genetics, Department of Pediatrics, Saint Justine Hospital, Montreal, Quebec, Canada., Lewis AJ; Pediatric Neurology, Kaiser Permanente Santa Clara Medical Center, Santa Clara, California, USA., Zweier C; Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.; Department of Human Genetics, Inselspital University Hospital Bern, Bern, BE, Switzerland., Reis A; Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany., Wagner M; Institute of Human Genetics, Technische Universitat Munchen, Munchen, Bayern, Germany.; Institute of Neurogenomics, Helmholtz Zentrum Munchen Deutsches Forschungszentrum fur Umwelt und Gesundheit, Neuherberg, Bayern, Germany., Weigand H; Division of Pediatric Neurology, Developmental Medicine and Social Pediatrics, Department of Pediatrics, Dr von Hauner Children's Hospital, Munich University Hospital (Ludwig Maximilians University), Munchen, Bayern, Germany., Journel H; Service de Génétique Médicale, Hopital Chubert, Vannes, Bretagne, France., Keren B; Département de Génétique et de Cytogénétique, Centre de Reference Déficience Intellectuelle de Causes Rares, GRC UPMC « Déficience Intellectuelle et Autisme », Hôpital Universitaire Pitié Salpêtrière, Paris, Île-de-France, France.; INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Épinière, Paris, Île-de-France, France., Passemard S; APHP, Hopital Universitaire Robert-Debre Departement de genetique, Paris, Île-de-France, France.; NeuroDiderot, UMR1141, INSERM, Paris, France., Mignot C; Département de Génétique et de Cytogénétique, Centre de Reference Déficience Intellectuelle de Causes Rares, GRC UPMC « Déficience Intellectuelle et Autisme », Hôpital Universitaire Pitié Salpêtrière, Paris, Île-de-France, France.; INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle Épinière, Paris, Île-de-France, France., van Gassen K; Department of Genetics, University Medical Centre Utrecht Center for Molecular Medicine, Utrecht, The Netherlands., Brilstra EH; Department of Genetics, University Medical Centre Utrecht Center for Molecular Medicine, Utrecht, The Netherlands., Itzikowitz G; Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, Rondebosch, Western Cape, South Africa., O'Heir E; Center for Mendelian Genomics and Program in Medical and Population Genetics, Broad Institute for Genome Research, Cambridge, Massachusetts, USA.; Division of Genetics and Genomics, Boston Children's Hospital, Boston, Massachusetts, USA., Allen J; Stanley Center for Psychiatric Research, Broad Institute Stanley Center for Psychiatric Research, Cambridge, Massachusetts, USA., Donald KA; Department of Paediatrics and Child Health, Red Cross War Memorial Children's Hospital, Rondebosch, Western Cape, South Africa.; Neuroscience Institute, University of Cape Town, Rondebosch, Western Cape, South Africa., Korf BR; 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Section of Genetics and Metabolism, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA., Alembik Y; Institut de génétique médicale d'Alsace (IGMA), Service de Génétique Médicale, Hôpitaux universitaires de Strasbourg, Strasbourg, Alsace, France., Durand B; Institut de génétique médicale d'Alsace (IGMA), Service de Génétique Médicale, Hôpitaux universitaires de Strasbourg, Strasbourg, Alsace, France., Tran Mau-Them F; Institut de génétique médicale d'Alsace (IGMA), Laboratoire de Diagnostic Génétique, Hôpitaux universitaires de Strasbourg, Strasbourg, Alsace, France., Ranza E; Medigenome, Swiss Institute of Medicine, Bern, Bern, Switzerland., Blanc X; Medigenome, Swiss Institute of Medicine, Bern, Bern, Switzerland., Antonarakis SE; Medigenome, Swiss Institute of Medicine, Bern, Bern, Switzerland., McWalter K; GeneDx, GeneDx, Gaithersburg, Maryland, USA., Torti E; GeneDx, GeneDx, Gaithersburg, Maryland, USA., Millan F; GeneDx, GeneDx, Gaithersburg, Maryland, USA., Dameron A; GeneDx, GeneDx, Gaithersburg, Maryland, USA., Tokita M; GeneDx, GeneDx, Gaithersburg, Maryland, USA., Zimmermann MT; Bioinformatics Research and Development Laboratory, Genomics Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.; Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA., Klee EW; Department of Quantitative Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA.; Center for Individualized Medicine, Mayo Clinic, Rochester, Minnesota, USA.; Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA., Piton A; Neurogenetics and Translational Medecine, Institut of Genetics and Molecular and Cellular Biology, Illkirch-Grafenstaden, Grand Est, France piton@igbmc.fr., Gerard B; Institut de génétique médicale d'Alsace (IGMA), Laboratoire de Diagnostic Génétique, Hôpitaux universitaires de Strasbourg, Strasbourg, Alsace, France. |
| المصدر: | Journal of medical genetics [J Med Genet] 2022 Oct; Vol. 59 (10), pp. 965-975. Date of Electronic Publication: 2021 Dec 15. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural |
| اللغة: | English |
| بيانات الدورية: | Publisher: British Medical Association Country of Publication: England NLM ID: 2985087R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1468-6244 (Electronic) Linking ISSN: 00222593 NLM ISO Abbreviation: J Med Genet Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: London : British Medical Association |
| مواضيع طبية MeSH: | Intellectual Disability*/genetics , Intellectual Disability*/pathology , Neurodevelopmental Disorders*/genetics , Neurodevelopmental Disorders*/pathology , Argonaute Proteins*/genetics, Humans ; Amino Acids/genetics ; Heterozygote ; RNA, Messenger |
| مستخلص: | Background: High-impact pathogenic variants in more than a thousand genes are involved in Mendelian forms of neurodevelopmental disorders (NDD). Methods: This study describes the molecular and clinical characterisation of 28 probands with NDD harbouring heterozygous AGO1 coding variants, occurring de novo for all those whose transmission could have been verified (26/28). Results: A total of 15 unique variants leading to amino acid changes or deletions were identified: 12 missense variants, two in-frame deletions of one codon, and one canonical splice variant leading to a deletion of two amino acid residues. Recurrently identified variants were present in several unrelated individuals: p.(Phe180del), p.(Leu190Pro), p.(Leu190Arg), p.(Gly199Ser), p.(Val254Ile) and p.(Glu376del). AGO1 encodes the Argonaute 1 protein, which functions in gene-silencing pathways mediated by small non-coding RNAs. Three-dimensional protein structure predictions suggest that these variants might alter the flexibility of the AGO1 linker domains, which likely would impair its function in mRNA processing. Affected individuals present with intellectual disability of varying severity, as well as speech and motor delay, autistic behaviour and additional behavioural manifestations. Conclusion: Our study establishes that de novo coding variants in AGO1 are involved in a novel monogenic form of NDD, highly similar to the recently reported AGO2 -related NDD. Competing Interests: Competing interests: KMW, ET, FM, AD and MJT are employees of GeneDx. ZP and KM are employees of Ambry Genetics. (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.) |
| معلومات مُعتمدة: | R01 AA026834 United States AA NIAAA NIH HHS; U01 MH119689 United States MH NIMH NIH HHS |
| فهرسة مساهمة: | Keywords: genetics; medical; microRNA; missense; mutation; nervous system diseases |
| المشرفين على المادة: | 0 (Amino Acids) 0 (RNA, Messenger) 0 (AGO1 protein, human) 0 (Argonaute Proteins) |
| تواريخ الأحداث: | Date Created: 20211221 Date Completed: 20221024 Latest Revision: 20231002 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC9241146 |
| DOI: | 10.1136/jmedgenet-2021-107751 |
| PMID: | 34930816 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1468-6244 |
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| DOI: | 10.1136/jmedgenet-2021-107751 |