UNIGE document Scientific Article
previous document  unige:96873  next document
add to browser collection
Title

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

Authors
Rudolf, Gabrielle
Lesca, Gaetan
Mehrjouy, Mana M
Labalme, Audrey
Salmi, Manal
Bache, Iben
Bruneau, Nadine
Pendziwiat, Manuela
show hidden authors show all authors [1 - 41]
Published in European Journal of Human Genetics. 2016, vol. 24, no. 12, p. 1761-1770
Abstract 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.
Keywords AdultChildChromosome BreakpointsChromosome DeletionCodon, NonsenseDevelopmental Disabilities/diagnosis/geneticsEpilepsy, Generalized/diagnosis/geneticsExomeExonsFemaleHumansMaleNuclear Receptor Subfamily 1, Group F, Member 2/geneticsPedigreeSyndromeTranslocation, Genetic
Identifiers
PMID: 27352968
Full text
Article (Published version) (2.1 MB) - document accessible for UNIGE members only Limited access to UNIGE
Structures
Citation
(ISO format)
RUDOLF, Gabrielle et al. Loss of function of the retinoid-related nuclear receptor (RORB) gene and epilepsy. In: European Journal of Human Genetics, 2016, vol. 24, n° 12, p. 1761-1770. https://archive-ouverte.unige.ch/unige:96873

60 hits

0 download

Update

Deposited on : 2017-09-19

Export document
Format :
Citation style :