Atrophin protein <scp>RERE</scp> positively regulates Notch targets in the developing vertebrate spinal cord

Wang, Hui; Gui, Hongxing; Rallo, Michael S.; Xu, Zhiyan; Matise, Michael P.

doi:10.1111/jnc.13969

Cited by 9 publications

(11 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, a recent report indicates that RERE and its Drosophila homolog associate with histone methyltransferases to regulate gene expression 25. MDD is a polygenic and multifactorial disease, and gene–environment interactions play a pivotal role in its pathophysiology.…”

Section: Discussionmentioning

confidence: 99%

Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms

Kakeda

Watanabe

Katsuki

et al. 2019

NDT

View full text Add to dashboard Cite

BackgroundA genome-wide association study using megadata identified 17 single-nucleotide polymorphisms (SNPs) in candidate genes for major depressive disorder (MDD). These MDD susceptibility polymorphisms may affect white matter (WM) integrity. This study aimed to investigate the relationship between WM alterations and 17 SNPs in candidate genes for MDD in the first depressive episode of drug-naive MDD patients using a tract-based spatial statistics (TBSS) method.MethodsThirty-five drug-naive MDD patients with a first depressive episode and 47 age-and sex-matched healthy subjects underwent diffusion tensor imaging scans and genotyping. The genotype–diagnosis interactions related to WM integrity were evaluated using TBSS for the 17 SNPs.ResultsFor the anterior thalamic radiation, cingulum, corticospinal tract, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, uncinate fasciculus, forceps major, and forceps minor, the genotype effect significantly differed between diagnosis groups (P<0.05, family-wise error corrected) in only one SNP, rs301806, in the arginine–glutamic acid dipeptide (RE) repeats (RERE) gene.ConclusionThe RERE polymorphism was associated with WM alterations in first-episode and drug-naive MDD patients, which may be at least partially related to the manifestation of MDD. Future studies are needed to explore the gene–environment interactions with regard to individual WM integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms

Kakeda

Watanabe

Katsuki

et al. 2019

NDT

View full text Add to dashboard Cite

show abstract

“…In addition, RERE has also been shown to stimulate Notch target gene expression, including the expression of Hes genes, by preventing degradation of the Notch intracellular domain (Wang, Gui, Rallo, Xu, & Matise, 2017). Similarly, CHD7 is required for the full induction of Hes5 in quiescent neural stem/progenitor cells and loss of CHD7 function leads to decreased expression of the Notch ligand JAG1 in the developing inner ear (Hurd, Micucci, Reamer, & Martin, 2012;Jones et al, 2015).…”

Section: Genotype-phenotype Correlationsmentioning

confidence: 99%

Genotype-phenotype correlations in individuals with pathogenicREREvariants

Jordan

Fregeau

et al. 2018

Human Mutation

View full text Add to dashboard Cite

Heterozygous variants in the arginine-glutamic acid dipeptide repeats gene (RERE) have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH who carry partial deletions or deleterious sequence variants in RERE. These variants were found to be de novo in all cases in which parental samples were available. An analysis of data from individuals with NEDBEH suggests that point mutations affecting the Atrophin-1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, renal anomalies, and sensorineural hearing loss when compared with loss-of-function variants that are likely to lead to haploinsufficiency. A high percentage of RERE pathogenic variants affect a histidine-rich region in the Atrophin-1 domain. We have also identified a recurrent two-amino-acid duplication in this region that is associated with the development of a CHARGE syndrome-like phenotype. We conclude that mutations affecting RERE result in a spectrum of clinical phenotypes. Genotype–phenotype correlations exist and can be used to guide medical decision making. Consideration should also be given to screening for RERE variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but do not carry pathogenic variants in CHD7.

show abstract

“…Thus, RERE may play a pivotal role in normal brain development 31,32. In addition, a recent report indicated that RERE and its Drosophila homolog were associated with histone methyltransferases in the regulation of gene expression 33. Gene–environment interactions play an essential role in MDD pathogenesis, which is a polygenic and heterogeneous disease.…”

Section: Discussionmentioning

confidence: 99%

A single-nucleotide polymorphism influences brain morphology in drug-naïve patients with major depressive disorder

Katsuki¹,

Kakeda²,

Watanabe³

et al. 2019

NDT

View full text Add to dashboard Cite

ObjectiveRecently, a genome-wide association study successfully identified genetic variants associated with major depressive disorder (MDD). The study identified 17 independent single-nucleotide polymorphisms (SNPs) significantly associated with diagnosis of MDD. These SNPs were predicted to be enriched in genes that are expressed in the central nervous system and function in transcriptional regulation associated with neurodevelopment. The study aimed to investigate associations between 17 SNPs and brain morphometry using magnetic resonance imaging (MRI) in drug-naïve patients with MDD and healthy controls (HCs).MethodsForty-seven patients with MDD and 42 HCs were included. All participants underwent T1-weighted structural MRI and genotyping. The genotype–diagnosis interactions associated with regional cortical thicknesses were evaluated using voxel-based morphometry for the 17 SNPs.ResultsRegarding rs301806, an SNP in the RERE genomic regions, we found a significant difference in a genotype effect in the right-lateral orbitofrontal and postcentral lobes between diagnosis groups. After testing every possible diagnostic comparison, the genotype–diagnosis interaction in these areas revealed that the cortical thickness reductions in the MDD group relative to those in the HC group were significantly larger in T/T individuals than in C-carrier ones. For the other SNPs, no brain area was noted where a genotype effect significantly differed between the two groups.ConclusionsWe found that a RERE gene SNP was associated with cortical thickness reductions in the right-lateral orbitofrontal and postcentral lobes in drug-naïve patients with MDD. The effects of RERE gene polymorphism and gene–environment interactions may exist in brain structures of patients with MDD.

show abstract

Atrophin protein RERE positively regulates Notch targets in the developing vertebrate spinal cord

Cited by 9 publications

References 48 publications

<p>Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms</p>

<p>Genetic effects on white matter integrity in drug-naive patients with major depressive disorder: a diffusion tensor imaging study of 17 genetic loci associated with depressive symptoms</p>

Genotype-phenotype correlations in individuals with pathogenicREREvariants

<p>A single-nucleotide polymorphism influences brain morphology in drug-naïve patients with major depressive disorder</p>

Contact Info

Product

Resources

About