Rare pathogenic variants in WNK3 cause X-linked intellectual disability

Sébastien Küry; Jinwei Zhang; Thomas Besnard; Alfonso Caro-Llopis; Xue Zeng; Stephanie M. Robert; Sunday S. Josiah; Emre Kiziltug; Anne-Sophie Denommé-Pichon; Benjamin Cogné; Adam J. Kundishora; Le T. Hao; Hong Li; Roger E. Stevenson; Raymond J. Louie; Wallid Deb; Erin Torti; Virginie Vignard; Kirsty McWalter; F. Lucy Raymond; Farrah Rajabi; Emmanuelle Ranza; Detelina Grozeva; Stephanie A. Coury; Xavier Blanc; Elise Brischoux-Boucher; Boris Keren; Katrin Õunap; Karit Reinson; Pilvi Ilves; Ingrid M. Wentzensen; Eileen E. Barr; Solveig Heide Guihard; Perrine Charles; Eleanor G. Seaby; Kristin G. Monaghan; Marlène Rio; Yolande van Bever; Marjon van Slegtenhorst; Wendy K. Chung; Ashley Wilson; Delphine Quinquis; Flora Bréhéret; Kyle Retterer; Pierre Lindenbaum; Emmanuel Scalais; Lindsay Rhodes; Katrien Stouffs; Elaine M. Pereira; Sara M. Berger; Sarah S. Milla; Ankita B. Jaykumar; Melanie H. Cobb; Shreyas Panchagnula; Phan Q. Duy; Marie Vincent; Sandra Mercier; Brigitte Gilbert-Dussardier; Xavier Le Guillou; Séverine Audebert-Bellanger; Sylvie Odent; Sébastien Schmitt; Pierre Boisseau; Dominique Bonneau; Annick Toutain; Estelle Colin; Laurent Pasquier; Richard Redon; Arjan Bouman; Jill. A. Rosenfeld; Michael J. Friez; Helena Pérez-Peña; Syed Raza Akhtar Rizvi; Shozeb Haider; Stylianos E. Antonarakis; Charles E. Schwartz; Francisco Martínez; Stéphane Bézieau; Kristopher T. Kahle; Bertrand Isidor

doi:10.1016/j.gim.2022.05.009

Retour

Rare pathogenic variants in WNK3 cause X-linked intellectual disability

Article de revue

Avec comité de lecture

Rare pathogenic variants in WNK3 cause X-linked intellectual disability

Sébastien Küry, Jinwei Zhang, Thomas Besnard, Alfonso Caro-Llopis, Xue Zeng, Stephanie M. Robert, Sunday S. Josiah, Emre Kiziltug, Anne-Sophie Denommé-Pichon, Benjamin Cogné, …

Genetics in medicine, Vol.24(9), pp.1941-1951

01/09/2022

DOI: https://doi.org/10.1016/j.gim.2022.05.009

PMID: 35678782

Résumé

Exome sequencing

KCC2

Neurodevelopmental disease

WNK3

X-linked intellectual disability

WNK3 kinase (PRKWNK3) has been implicated in the development and function of the brain via its regulation of the cation-chloride cotransporters, but the role of WNK3 in human development is unknown. We ascertained exome or genome sequences of individuals with rare familial or sporadic forms of intellectual disability (ID). We identified a total of 6 different maternally-inherited, hemizygous, 3 loss-of-function or 3 pathogenic missense variants (p.Pro204Arg, p.Leu300Ser, p.Glu607Val) in WNK3 in 14 male individuals from 6 unrelated families. Affected individuals had ID with variable presence of epilepsy and structural brain defects. WNK3 variants cosegregated with the disease in 3 different families with multiple affected individuals. This included 1 large family previously diagnosed with X-linked Prieto syndrome. WNK3 pathogenic missense variants localize to the catalytic domain and impede the inhibitory phosphorylation of the neuronal-specific chloride cotransporter KCC2 at threonine 1007, a site critically regulated during the development of synaptic inhibition. Pathogenic WNK3 variants cause a rare form of human X-linked ID with variable epilepsy and structural brain abnormalities and implicate impaired phospho-regulation of KCC2 as a pathogenic mechanism. [Display omitted]

Indicateurs

1 Consultations de la notice

See more details

Détails

Titre: Rare pathogenic variants in WNK3 cause X-linked intellectual disability
Créateurs - sans rôle: Sébastien Küry - Nantes Université
Jinwei Zhang - Hatherly Laboratories, The Institute of Biomedical and Clinical Sciences, College of Medicine and Health, University of Exeter, Exeter, United Kingdom
Thomas Besnard - Nantes Université
Alfonso Caro-Llopis - Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Xue Zeng - Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT
Stephanie M. Robert - Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT
Sunday S. Josiah - Hatherly Laboratories, The Institute of Biomedical and Clinical Sciences, College of Medicine and Health, University of Exeter, Exeter, United Kingdom
Emre Kiziltug - Department of Genetics, Yale School of Medicine, Yale University, New Haven, CT
Anne-Sophie Denommé-Pichon - Département de Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
Benjamin Cogné - Nantes Université
Adam J. Kundishora - Department of Neurosurgery, Yale School of Medicine, Yale University, New Haven, CT
Le T. Hao - Department of Neurosurgery, Yale School of Medicine, Yale University, New Haven, CT
Hong Li - Departments of Human Genetics and Pediatrics, School of Medicine, Emory University, Atlanta, GA
Roger E. Stevenson - Greenwood Genetic Center
Raymond J. Louie - Greenwood Genetic Center
Wallid Deb - Nantes Université
Erin Torti - GeneDx, Gaithersburg, MD
Virginie Vignard - Nantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France
Kirsty McWalter - GeneDx, Gaithersburg, MD
F. Lucy Raymond - University of Cambridge
Farrah Rajabi - Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA
Emmanuelle Ranza - Medigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland
Detelina Grozeva - Department of Medical Genetics, Cambridge Institute for Medical Research, University of Cambridge, Biomedical Campus Cambridge, Cambridge, United Kingdom
Stephanie A. Coury - Division of Genetics and Genomics, Boston Children’s Hospital, Boston, MA
Xavier Blanc - Medigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland
Elise Brischoux-Boucher - Université de Bourgogne
Boris Keren - Assistance Publique – Hôpitaux de Paris
Katrin Õunap - Tartu University Hospital
Karit Reinson - Department of Clinical Genetics, Genetics and Personalized Medicine Clinic, Tartu University Hospital, Tartu, Estonia
Pilvi Ilves - Department of Clinical Genetics, Institute of Clinical Medicine, Faculty of Medicine, University of Tartu, Tartu, Estonia
Ingrid M. Wentzensen - GeneDx, Gaithersburg, MD
Eileen E. Barr - Departments of Human Genetics and Pediatrics, School of Medicine, Emory University, Atlanta, GA
Solveig Heide Guihard - Department of Genetics, Centre de Référence Déficiences Intellectuelles de Causes Rares, Pitié-Salpêtrière Hospital, Assistance Publique-Hôpitaux de Paris, Paris, France
Perrine Charles - Assistance Publique – Hôpitaux de Paris
Eleanor G. Seaby - Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA
Kristin G. Monaghan - GeneDx, Gaithersburg, MD
Marlène Rio - Developmental Brain Disorders laboratory, INSERM UMR 1163, Imagine Institute, University of Paris, Paris, France
Yolande van Bever - Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
Marjon van Slegtenhorst - Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
Wendy K. Chung - Departments of Pediatrics and Medicine, Columbia University Irving Medical Center, Columbia University New York, NY
Ashley Wilson - Division of Clinical Genetics, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY
Delphine Quinquis - Nantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France
Flora Bréhéret - Nantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France
Kyle Retterer - GeneDx, Gaithersburg, MD
Pierre Lindenbaum - Institut du Thorax
Emmanuel Scalais - Centre Hospitalier de Luxembourg
Lindsay Rhodes - GeneDx, Gaithersburg, MD
Katrien Stouffs - Neurogenetics Research Group, Reproduction and Genetics, Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan, Brussels, Belgium
Elaine M. Pereira - Division of Clinical Genetics, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY
Sara M. Berger - Division of Clinical Genetics, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons and New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY
Sarah S. Milla - Department of Radiology and Imaging Sciences, School of Medicine, Emory University, Atlanta, GA
Ankita B. Jaykumar - Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX
Melanie H. Cobb - Department of Pharmacology, UT Southwestern Medical Center, Dallas, TX
Shreyas Panchagnula - Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Phan Q. Duy - Department of Neurosurgery, Yale School of Medicine, Yale University, New Haven, CT
Marie Vincent - Nantes Université
Sandra Mercier - Nantes Université
Brigitte Gilbert-Dussardier - Centre Hospitalier Universitaire de Poitiers
Xavier Le Guillou - Service de Génétique, CHU Poitiers, Poitiers, France
Séverine Audebert-Bellanger - Génétique Médicale, CHRU Brest, Brest, France
Sylvie Odent - ERN ITHACA
Sébastien Schmitt - Nantes Université
Pierre Boisseau - Nantes Université, CHU Nantes, Service de Génétique Médicale, Nantes, France
Dominique Bonneau - Département de Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
Annick Toutain - Unité de Génétique Médicale, Centre Hospitalier Régional Universitaire de Tours, France
Estelle Colin - Département de Biochimie et Génétique, Centre Hospitalier Universitaire Angers, Angers, France
Laurent Pasquier - ERN ITHACA
Richard Redon - Nantes Université, CHU Nantes, CNRS, INSERM, l’institut du thorax, Nantes, France
Arjan Bouman - Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands
Jill. A. Rosenfeld - Baylor College of Medicine
Michael J. Friez - Greenwood Genetic Center
Helena Pérez-Peña - Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, University College London, London, United Kingdom
Syed Raza Akhtar Rizvi - Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, University College London, London, United Kingdom
Shozeb Haider - Department of Pharmaceutical and Biological Chemistry, UCL School of Pharmacy, University College London, London, United Kingdom
Stylianos E. Antonarakis - Medigenome, Swiss Institute of Genomic Medicine, Geneva, Switzerland
Charles E. Schwartz - Greenwood Genetic Center, Greenwood, SC
Francisco Martínez - Unidad de Genética, Hospital Universitario y Politécnico La Fe, Valencia, Spain
Stéphane Bézieau - Nantes Université
Kristopher T. Kahle - Department of Neurosurgery, Yale School of Medicine, Yale University, New Haven, CT
Bertrand Isidor - Nantes Université
Détails de publication: Genetics in medicine, Vol.24(9), pp.1941-1951
Éditeur: Elsevier Inc
Identifiants: 99158812309311
Unité académique: Physiologie et Médecine Expérimentale du coeur et des muscles - PhyMedExp
Langue: English
Type de ressource: Journal article