RORB Research Articles

Retinoid-Related Orphan Receptor β and Transcriptional Control of Neuronal Differentiation.

The ability to generate neuronal diversity is central to the function of the nervous system. Here we discuss the key neurodevelopmental roles of retinoid-related orphan receptor β (RORβ) encoded by the Rorb (Nr1f2) gene. Recent studies have reported loss of function of the human RORB gene in cases of familial epilepsy and intellectual disability. Principal sites of expression of the Rorb gene in model species include sensory organs, the spinal cord, and brain regions that process sensory and circadian information. Genetic analyses in mice have indicated functions in circadian behavior, vision, and, at the cellular level, the differentiation of specific neuronal cell types. Studies in the retina and sensory areas of the cerebral cortex suggest that this orphan nuclear receptor acts at decisive steps in transcriptional hierarchies that determine neuronal diversity.

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

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.

RORB gene and 9q21.13 microdeletion: Report on a patient with epilepsy and mild intellectual disability

Copy number variants represent an important cause of neurodevelopmental disorders including epilepsy, which is genetically determined in 40% of cases. Epilepsy is caused by chromosomal imbalances or mutations in genes encoding subunits of neuronal voltage- or ligand-gated ion channels or proteins related to neuronal maturation and migration during embryonic development. Here, we report on a girl with mild intellectual disability and idiopathic partial epilepsy. Array-CGH analysis showed a 1.040 Mb de novo interstitial deletion at 9q21.13 band encompassing only four genes, namely RORB, TRPM6, NMRK1, OSTF1, two open reading frames (C9orf40, C9orf41), and a microRNA (MIR548H3). RORB encodes a nuclear receptor highly expressed in the retina, cortex, and thalamus. We hypothesize its role in producing the phenotype of our patient and compare this case with other ones previously reported in the literature to better identify a genotype–phenotype correlation.

Differential Expression of Various T Cell Surface Markers in Young and Elderly Subjects

The purpose of this study was to investigate the expression of lymphocyte markers in the peripheral blood of aged individuals and of young healthy blood donors. Results showed significant changes in the distribution of various T cell subpopulations. The CD3, CD4 and CD8 surface expression was not different in the elderly patients when compared to the young subjects. The number of CD4 + T cells expressing CD45 RO isoform (memory cells) was increased in aged people; CD45 RA + CD4 + cells (naive cells) were decreased. The expression of the CD45 RB on the CD4 + cells was significantly lower in the elderly when compared to the young subjects. In contrast, the surface expression of CD45 RO and CD45 RB in the CD8 + cells was not statistically different in the young and aged subjects. The proportion of CD8 + cells coexpressing CD57 was significantly increased in the elderly subjects. These results indicate age-dependent alterations of various surface markers of T cells. These observations may be of importance in the investigation of immunoregulatory mechanisms in geriatric patients with infection, autoimmune disease or cancer.

The cloning of the rorB gene of Escherichia coli.

A segment of the Escherichia coli genome which complements the ionising radiation sensitivity of the rorB mutation was cloned into pBR322. This DNA segment also complements the mitomycin C sensitivity of the rorB mutation. The gene was subcloned until defined in a fragment of 1.05 kb. Only one gene product, a protein of approximately 16.5 kDa, was found on maxicell analysis of the various subclones. Iso-electric focusing of this gene product suggests it may function in a complex.

The isolation and preliminary characterisation of a novel Escherichia coli mutant rorB with enhanced sensitivity to ionising radiation.

Escherichia coli K803 cells were mutagenized and screened for the presence of clones sensitive to gamma-rays but not to ultraviolet light. One new mutant of this type, named rorB, was isolated. This mutant is both cross-sensitive to mitomycin C and shows reduced conjugal recombination frequencies, but to a lesser extent than the phenotypically similar mutant recN. Unlike previously reported mutants of E. coli or yeast with an enhanced sensitivity to ionising radiations, rorB appears to be near wild type in ability to rejoin DNA double-strand breaks. The rorB gene maps close to ilvGEDAC at 84.5 min of the E. coli chromosome.