IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients

Cyril Mignot; Aoife Mcmahon; Claire Bar; Philippe Campeau; David Davidson; Julien Buratti; Caroline Nava; Marie-Line Jacquemont; Marilyn Tallot; Mathieu Milh; Patrick Edery; Pauline Marzin; Giulia Barcia; Christine Barnerias; Claude Besmond; Thierry Bienvenu; Ange-Line Bruel; Ledia Brunga; Berten Ceulemans; Christine Coubes; Ana Cristancho; Fiona Cunningham; Marie-Bertille Dehouck; Elizabeth Donner; Bénédicte Duban-Bedu; Christèle Dubourg; Elena Gardella; Julie Gauthier; David Genevieve; Stéphanie Gobin-Limballe; Ethan Goldberg; Eveline Hagebeuk; Fadi Hamdan; Miroslava Hančárová; Laurence Hubert; Christine Ioos; Shoji Ichikawa; Sandra Janssens; Hubert Journel; Anna Kaminska; Boris Keren; Marije Koopmans; Caroline Lacoste; Petra Laššuthová; Damien Lederer; Daphne Lehalle; Dragan Marjanovic; Julia Metreau; Jacques Michaud; Kathryn Miller; Berge Minassian; Joannella Morales; Marie-Laure Moutard; Arnold Munnich; Xilma Ortiz-Gonzalez; Jean-Marc Pinard; Darina Prchalová; Audrey Putoux; Chloé Quélin; Alyssa Rosen; Joëlle Roume; Elsa Rossignol; Marleen Simon; Thomas Smol; Natasha Shur; Ivan Shelihan; Katalin Štěrbová; Emílie Vyhnálková; Catheline Vilain; Julie Soblet; Guillaume Smits; Samuel Yang; Jasper van Der Smagt; Peter van Hasselt; Marjan van Kempen; Sarah Weckhuysen; Ingo Helbig; Laurent Villard; Delphine Héron; Bobby Koeleman; Rikke Møller; Gaetan Lesca; Katherine L. Helbig; Rima Nabbout; Nienke E. Verbeek; Christel Depienne

doi:10.1038/s41436-018-0268-1

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IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients

Journal article

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IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients

Cyril Mignot, Aoife Mcmahon, Claire Bar, Philippe Campeau, David Davidson, Julien Buratti, Caroline Nava, Marie-Line Jacquemont, Marilyn Tallot, Mathieu Milh, …

Genetics in Medicine, Vol.21(8), pp.1897-1898

04/2019

DOI: https://doi.org/10.1038/s41436-018-0268-1

PMID: 30206421

Abstract

intellectual disability

isoforms

epilepsy

X-linked inheritance

IQSEC2

Purpose: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences.Methods: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms.Results: IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments.Conclusion: This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.

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Title: IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients
Creators - without role: Cyril Mignot - Sorbonne Université
Aoife Mcmahon - European Bioinformatics Institute
Claire Bar - Institut des Maladies Génétiques Imagine
Philippe Campeau - Université de Montréal
David Davidson - European Bioinformatics Institute
Julien Buratti - Centre d'Épidémiologie sur les Causes Médicales de Décès
Caroline Nava - Centre d'Épidémiologie sur les Causes Médicales de Décès
Marie-Line Jacquemont - Centre Hospitalier Universitaire de La Réunion
Marilyn Tallot - Centre Hospitalier Universitaire de La Réunion
Mathieu Milh - Inserm
Patrick Edery - Université Claude Bernard Lyon 1
Pauline Marzin - Sorbonne Université
Giulia Barcia - Université Paris Cité
Christine Barnerias - Université Paris Cité
Claude Besmond - Université Paris Cité
Thierry Bienvenu - Hôpital Cochin
Ange-Line Bruel - Inserm
Ledia Brunga - University of Toronto
Berten Ceulemans - University of Antwerp
Christine Coubes - Département de génétique médicale, maladies rares et médecine personnalisée [CHU Montpellier]
Ana Cristancho - Children's Hospital of Philadelphia
Fiona Cunningham - European Bioinformatics Institute
Marie-Bertille Dehouck - Hôpital Saint-Vincent-de-Paul
Elizabeth Donner - University of Toronto
Bénédicte Duban-Bedu - Hôpital Saint-Vincent-de-Paul
Christèle Dubourg - Centre Hospitalier Universitaire de Rennes
Elena Gardella - University of Southern Denmark
Julie Gauthier - Centre Hospitalier Universitaire Sainte-Justine
David Genevieve - Inserm
Stéphanie Gobin-Limballe - Assistance Publique – Hôpitaux de Paris
Ethan Goldberg - Children's Hospital of Philadelphia
Eveline Hagebeuk - Stichting Epilepsie Instellingen Nederland
Fadi Hamdan - Université de Montréal
Miroslava Hančárová - Charles University
Laurence Hubert - Inserm
Christine Ioos - Hôpital Raymond-Poincaré
Shoji Ichikawa - Ambry Genetics
Sandra Janssens - Ghent University Hospital
Hubert Journel
Anna Kaminska - Institut Necker Enfants Malades
Boris Keren - Sorbonne Université
Marije Koopmans - University Medical Center [Utrecht]
Caroline Lacoste - Hôpital de la Timone
Petra Laššuthová - Charles University
Damien Lederer - Institute of Pathology and Genetics
Daphne Lehalle - Hôpital Intercommunal de Créteil
Dragan Marjanovic - Filadelfia
Julia Metreau - Bicêtre Hospital
Jacques Michaud - Centre Hospitalier Universitaire Sainte-Justine
Kathryn Miller - Albany Medical Center Hospital
Berge Minassian - University of Toronto
Joannella Morales - European Bioinformatics Institute
Marie-Laure Moutard - Charmo University
Arnold Munnich - Inserm
Xilma Ortiz-Gonzalez - Children's Hospital of Philadelphia
Jean-Marc Pinard - Hôpital Raymond-Poincaré
Darina Prchalová - Charles University
Audrey Putoux - Hospices Civils de Lyon
Chloé Quélin - Hôpital Nord
Alyssa Rosen - Children's Hospital of Philadelphia
Joëlle Roume - Centre Hospitalier Intercommunal de Poissy
Elsa Rossignol - Centre Hospitalier Universitaire Sainte-Justine
Marleen Simon - University Medical Center Utrecht
Thomas Smol - Université de Lille
Natasha Shur - Albany Medical Center Hospital
Ivan Shelihan - Centre Hospitalier Universitaire Sainte-Justine
Katalin Štěrbová - Charles University
Emílie Vyhnálková - Charles University
Catheline Vilain - Erasmus Hospital
Julie Soblet - Université Libre de Bruxelles
Guillaume Smits - Université Libre de Bruxelles
Samuel Yang - Providence Regional Medical Center Everett
Jasper van Der Smagt - University Medical Center Utrecht
Peter van Hasselt - Wilhelmina Children's Hospital
Marjan van Kempen - University Medical Center Utrecht
Sarah Weckhuysen - VIB-UAntwerp Center for Molecular Neurology
Ingo Helbig - Children's Hospital of Philadelphia
Laurent Villard - Inserm
Delphine Héron - Centre d'Épidémiologie sur les Causes Médicales de Décès
Bobby Koeleman - University Medical Center [Utrecht]
Rikke Møller - Centre Hospitalier Universitaire de Rennes
Gaetan Lesca - Inserm
Katherine L. Helbig - Children's Hospital of Philadelphia
Rima Nabbout - Université Paris Cité
Nienke E. Verbeek - University Medical Center Utrecht
Christel Depienne - Centre National de la Recherche Scientifique
Publication Details: Genetics in Medicine, Vol.21(8), pp.1897-1898
Identifiers: 9941135609311
Academic Unit: Cell souches plasticité cellul régénérat tissulaire immuno des maladies inflamm - IRMB
Language: English
Resource Type: Journal article
Local Fields: hal-01919142