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Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy.

  • Rudolf G IGBMC, CNRS UMR7104, INSERM U964, Strasbourg University, Strasbourg, France.
  • Lesca G Department of Genetics, Lyon University Hospitals, Lyon, France.
  • Mehrjouy MM Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
  • Labalme A Department of Genetics, Lyon University Hospitals, Lyon, France.
  • Salmi M INSERM U901, Marseille, France.
  • Bache I Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
  • Bruneau N INSERM U901, Marseille, France.
  • Pendziwiat M Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.
  • Fluss J Pediatric Neurology, Child and Adolescent Department, Geneva University Hospitals, Geneva, Switzerland.
  • de Bellescize J Epilepsy, Sleep and Pediatric Neurophysiology Department, Lyon University Hospitals, Lyon, France.
  • Scholly J Department of Neurology, Strasbourg University Hospital, Strasbourg, France.
  • Møller RS Danish Epilepsy Centre, Dianalund, Denmark.
  • Craiu D "Carol Davila" University of Medicine Bucharest, Department of Clinical Neurosciences (No.6), Pediatric Neurology Clinic, Alexandru Obregia Hospital, Bucharest, Romania.
  • Tommerup N Department of Cellular and Molecular Medicine, Wilhelm Johannsen Centre for Functional Genome Research, University of Copenhagen, Copenhagen, Denmark.
  • Valenti-Hirsch MP Department of Neurology, Strasbourg University Hospital, Strasbourg, France.
  • Schluth-Bolard C Department of Genetics, Lyon University Hospitals, Lyon, France.
  • Sloan-Béna F Department of Medical Genetics, University Hospitals of Geneva, Geneva, Switzerland.
  • Helbig KL Division of Clinical Genomics, Ambry Genetics, Aliso Viejo, CA, USA.
  • Weckhuysen S Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
  • Edery P Department of Genetics, Lyon University Hospitals, Lyon, France.
  • Coulbaut S UCB-Pharma, Colombes, France.
  • Abbas M UCB-Pharma, Colombes, France.
  • Scheffer IE Florey Institute, University of Melbourne, Austin Health and Royal Children's Hospital, Melbourne, Australia.
  • Tang S Division of Clinical Genomics, Ambry Genetics, Aliso Viejo, CA, USA.
  • Myers CT Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, USA.
  • Stamberger H Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.
  • Carvill GL Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, USA.
  • Shinde DN Division of Clinical Genomics, Ambry Genetics, Aliso Viejo, CA, USA.
  • Mefford HC Department of Pediatrics, Division of Genetic Medicine, University of Washington, Seattle, USA.
  • Neagu E Human Genetics Laboratory, "Mina Minovici" National Institute of Forensic Medicine, Bucharest, Romania.
  • Huether R Department of Bioinformatics, Ambry Genetics, Aliso Viejo, CA, USA.
  • Lu HM Department of Bioinformatics, Ambry Genetics, Aliso Viejo, CA, USA.
  • Dica A "Carol Davila" University of Medicine Bucharest, Department of Clinical Neurosciences (No.6), Pediatric Neurology Clinic, Alexandru Obregia Hospital, Bucharest, Romania.
  • Cohen JS Department of Neurology and Developmental Medicine, Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
  • Iliescu C "Carol Davila" University of Medicine Bucharest, Department of Clinical Neurosciences (No.6), Pediatric Neurology Clinic, Alexandru Obregia Hospital, Bucharest, Romania.
  • Pomeran C "Carol Davila" University of Medicine Bucharest, Department of Clinical Neurosciences (No.6), Pediatric Neurology Clinic, Alexandru Obregia Hospital, Bucharest, Romania.
  • Rubenstein J Department of Neurology and Developmental Medicine, Division of Neurogenetics, Kennedy Krieger Institute, Baltimore, MD, USA.
  • Helbig I Department of Neuropediatrics, Christian-Albrechts-University of Kiel and University Medical Center Schleswig-Holstein (UKSH), Kiel, Germany.
  • Sanlaville D Department of Genetics, Lyon University Hospitals, Lyon, France.
  • Hirsch E IGBMC, CNRS UMR7104, INSERM U964, Strasbourg University, Strasbourg, France.
  • Szepetowski P INSERM U901, Marseille, France.
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  • 2016-06-30
Published in:
  • European journal of human genetics : EJHG. - 2016
Adult
Child
Chromosome Breakpoints
Chromosome Deletion
Codon, Nonsense
Developmental Disabilities
Epilepsy, Generalized
Exome
Exons
Female
Humans
Male
Nuclear Receptor Subfamily 1, Group F, Member 2
Pedigree
Syndrome
Translocation, Genetic
English Genetic generalized epilepsy (GGE), formerly known as idiopathic generalized epilepsy, is the most common form of epilepsy and is thought to have predominant genetic etiology. GGE are clinically characterized by absence, myoclonic, or generalized tonic-clonic seizures with electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and-wave discharges. Despite their strong heritability, the genetic basis of generalized epilepsies remains largely elusive. Nevertheless, recent advances in genetic technology have led to the identification of numerous genes and genomic defects in various types of epilepsies in the past few years. In the present study, we performed whole-exome sequencing in a family with GGE consistent with the diagnosis of eyelid myoclonia with absences. We found a nonsense variant (c.196C>T/p.(Arg66*)) in RORB, which encodes the beta retinoid-related orphan nuclear receptor (RORβ), in four affected family members. In addition, two de novo variants (c.218T>C/p.(Leu73Pro); c.1249_1251delACG/p.(Thr417del)) were identified in sporadic patients by trio-based exome sequencing. We also found two de novo deletions in patients with behavioral and cognitive impairment and epilepsy: a 52-kb microdeletion involving exons 5-10 of RORB and a larger 9q21-microdeletion. Furthermore, we identified a patient with intellectual disability and a balanced translocation where one breakpoint truncates RORB and refined the phenotype of a recently reported patient with RORB deletion. Our data support the role of RORB gene variants/CNVs in neurodevelopmental disorders including epilepsy, and especially in generalized epilepsies with predominant absence seizures.
Language
  • English
Open access status
bronze
Identifiers
Persistent URL
https://sonar.ch/global/documents/229562
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