ADGRL1 haploinsufficiency causes a variable spectrum of neurodevelopmental disorders in humans and alters synaptic activity and behavior in a mouse model.

ADGRL1 ADHD ASD Adgrl1 knockout mice attention deficit hyperactivity disorder autism spectrum disorder developmental delay epilepsy intellectual disability malfunctional behavior in mice neuropsychiatric disorders variable expressivity

Journal

American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475

Informations de publication

Date de publication:
04 08 2022
Historique:
received: 06 04 2022
accepted: 22 06 2022
pubmed: 31 7 2022
medline: 10 8 2022
entrez: 30 7 2022
Statut: ppublish

Résumé

ADGRL1 (latrophilin 1), a well-characterized adhesion G protein-coupled receptor, has been implicated in synaptic development, maturation, and activity. However, the role of ADGRL1 in human disease has been elusive. Here, we describe ten individuals with variable neurodevelopmental features including developmental delay, intellectual disability, attention deficit hyperactivity and autism spectrum disorders, and epilepsy, all heterozygous for variants in ADGRL1. In vitro, human ADGRL1 variants expressed in neuroblastoma cells showed faulty ligand-induced regulation of intracellular Ca

Identifiants

pubmed: 35907405
pii: S0002-9297(22)00264-6
doi: 10.1016/j.ajhg.2022.06.011
pmc: PMC9388395
pii:
doi:

Substances chimiques

ADGRL1 protein, human 0
Adgrl1 protein, mouse 0
Receptors, G-Protein-Coupled 0
Receptors, Peptide 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1436-1457

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BBD523078
Pays : United Kingdom
Organisme : Wellcome Trust
ID : GR074359MA
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Wellcome Trust
ID : WT083199MF
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBF0083091
Pays : United Kingdom

Informations de copyright

Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratories. A.C. is an employee of GeneDx, Inc.

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Auteurs

Antonio Vitobello (A)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France. Electronic address: antonio.vitobello@u-bourgogne.fr.

Benoit Mazel (B)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France; Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD - CHU Dijon Bourgogne, Dijon, France.

Vera G Lelianova (VG)

Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham ME4 4TB, UK; Department of Life Sciences, Imperial College London, London, UK.

Alice Zangrandi (A)

Department of Life Sciences, Imperial College London, London, UK.

Evelina Petitto (E)

Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham ME4 4TB, UK.

Jason Suckling (J)

Department of Life Sciences, Imperial College London, London, UK.

Vincenzo Salpietro (V)

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy.

Robert Meyer (R)

Institute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, Germany.

Miriam Elbracht (M)

Institute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, Germany.

Ingo Kurth (I)

Institute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, Germany.

Thomas Eggermann (T)

Institute of Human Genetics, Medical Faculty, RWTH Aachen, Aachen, Germany.

Ouafa Benlaouer (O)

Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham ME4 4TB, UK.

Gurprit Lall (G)

Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham ME4 4TB, UK.

Alexander G Tonevitsky (AG)

Faculty of Biology and Biotechnology, HSE University, Moscow, Russia; Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997, Moscow, Russia.

Daryl A Scott (DA)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Katie M Chan (KM)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Jill A Rosenfeld (JA)

Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.

Sophie Nambot (S)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD - CHU Dijon Bourgogne, Dijon, France.

Hana Safraou (H)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.

Ange-Line Bruel (AL)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.

Anne-Sophie Denommé-Pichon (AS)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.

Frédéric Tran Mau-Them (F)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.

Christophe Philippe (C)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.

Yannis Duffourd (Y)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France.

Hui Guo (H)

Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China; Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA, USA.

Andrea K Petersen (AK)

Randall Children's Hospital, Portland, OR, USA.

Leslie Granger (L)

Randall Children's Hospital, Portland, OR, USA.

Amy Crunk (A)

GeneDx, Inc., Gaithersburg, MD, USA.

Allan Bayat (A)

Department of Epilepsy Genetics and Personalized Medicine, Danish Epilepsy Centre, Dianalund, Denmark; Department of Regional Health Research, University of Southern Denmark, Odense, Denmark.

Pasquale Striano (P)

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Federico Zara (F)

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Medical Genetics Unit, IRCSS Istituto Giannina Gastini, Genoa, Italy.

Marcello Scala (M)

Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, Genoa, Italy; Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.

Quentin Thomas (Q)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; Centre de Génétique et Centre de Référence Déficiences Intellectuelles de causes rares, FHU TRANSLAD - CHU Dijon Bourgogne, Dijon, France.

Andrée Delahaye (A)

UF médecine génomique et génétique clinique, Hôpital Jean Verdier, Hôpitaux Universitaires de Paris Seine Saint Denis, AP-HP, Bondy, France; UFR de Santé Médecine et Biologie humaine, Université Sorbonne Paris Nord, Bodigny, France; NeuroDiderot UMR 1141, Inserm, FHU I2-D2, Université de Paris, Paris, France.

Jean-Madeleine de Sainte Agathe (JM)

Département de Génétique Médicale, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France.

Julien Buratti (J)

Département de Génétique Médicale, Hôpital Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France.

Serguei V Kozlov (SV)

Center for Advanced Preclinical Research, National Cancer Institute, Frederick, MD, USA.

Laurence Faivre (L)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; Centre de Génétique et Centre de Référence Anomalies du Développement et Syndromes Malformatifs, FHU TRANSLAD - CHU Dijon Bourgogne, Dijon, France.

Christel Thauvin-Robinet (C)

Inserm UMR1231 GAD, Génétique des Anomalies du Développement, Fédération Hospitalo-Universitaire Médecine Translationnelle et Anomalies du Développement (FHU TRANSLAD), CHU Dijon Bourgogne - Université de Bourgogne, Dijon, France; UF Innovation en diagnostic génomique des maladies rares, CHU Dijon Bourgogne, Dijon, France; Centre de Génétique et Centre de Référence Déficiences Intellectuelles de causes rares, FHU TRANSLAD - CHU Dijon Bourgogne, Dijon, France.

Yuri Ushkaryov (Y)

Medway School of Pharmacy, University of Kent, Anson Building, Central Avenue, Chatham ME4 4TB, UK; Department of Life Sciences, Imperial College London, London, UK; Faculty of Biology and Biotechnology, HSE University, Moscow, Russia. Electronic address: y.ushkaryov@kent.ac.uk.

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