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

2016
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 seizureswith electroencephalographic pattern of bilateral, synchronous, and symmetrical spike-and- wavedischarges. Despite their strong heritability, the genetic basis of generalized epilepsiesremains 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 sequencingin 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 disordersincluding epilepsy, and especially in generalized epilepsieswith predominant absence seizures.
    • Correction
    • Source
    • Cite
    • Save
    30
    References
    20
    Citations
    NaN
    KQI
    []
    Baidu
    map