A fetus 'at-risk' for ataxia telangiectasia (A-T) was monitored prenatally by several approaches which, in concert, might yield information of diagnostic value: measurement of amniotic fluid AFP levels; the clastogenic potential of 'at-risk' amniotic fluid; and cytogenic evaluation of fetal amniocytes.
Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by cerebellar ataxia, telangiectasia, immunodeficiency, elevated alpha-fetoprotein levels, chromosomal instability, predisposition to cancer, and radiation sensitivity.
Tissue transglutaminase (TG2), a potent cross-linking enzyme, is known to be transcriptionally activated by inflammatory cytokines and stabilize angiotensin II (Ang II) receptor AT1 (AT1R) via ubiquitination-preventing posttranslational modification.
In the fetal portion of the placenta, AngII in the FP, PF and PP groups and AT2R in the PF and PP groups were decreased, but AT1R was increased in the FP group.
In the present study, we reveal the adipogenic effects of Ang(1-7) through activation of Mas receptor and its subtle interplays with the antiadipogenic AngII-AT1 signaling pathways.
Our in vitro cellular assays showed that LIGHT stimulation triggered a rapid TG2-dependent increase in the abundance of AT1Rs (relative AT1R level after 2-hour LIGHT treatment: AT1R (WT)+TG2 = 2.21 ± 0.23, AT1R (Q315A)+TG2 = 0.18 ± 0.23, P < 0.05 vs. starting point = 1, n = 2) and downstream calcium signaling (fold increase in NFAT-driven luciferase activity: Saline = 0.02 ± 0.03, Ang II = 0.17 ± 0.08, LIGHT = 0.05 ± 0.04, LIGHT+Ang II = 0.90 ± 0.04 (P < 0.01 vs. Ang II), and LIGHT+Ang II+ERW1041E = 0.15 ± 0.15 (P < 0.01 vs. LIGHT+Ang II), n = 3).
Twenty-two patients with the classic phenotype of ataxia-telangiectasia were grouped into early stage cerebellar disease (group AT-I) versus late stage cerebrocerebellar disease (group AT-II) and examined for neurocognitive features.
AKT is activated in an ataxia-telangiectasia and Rad3-related-dependent manner in response to temozolomide and confers protection against drug-induced cell growth inhibition.
Mutations of Ras, PIK3Ca, PTEN, and BRAF genes and RET/PTC rearrangements were common, whereas mutations in PDK1, Akt1, Akt2, and RTK genes were uncommon in ATC.
However, the frequency of the ALOX5-ht1[G-C-G-A] haplotype in the AIA group was significantly higher than its frequency in the ATA group with a probability ( P) of 0.01, odds ratio (OR) of 5.0, and 95% confidence interval (95%CI) of 1.54-17.9, and in the normal controls ( P=0.03, OR=4.5, 95%CI=1.1-18.4), by using a dominant model.
In the present study, we reveal the adipogenic effects of Ang(1-7) through activation of Mas receptor and its subtle interplays with the antiadipogenic AngII-AT1 signaling pathways.
Tissue transglutaminase (TG2), a potent cross-linking enzyme, is known to be transcriptionally activated by inflammatory cytokines and stabilize angiotensin II (Ang II) receptor AT1 (AT1R) via ubiquitination-preventing posttranslational modification.
Among regions with multiple potential candidates is chromosome 11, which includes the apolipoprotein C3 cluster, muscle glycogen phosphorylase, two insulin-dependent diabetes loci, the sulfonylurea receptor, and ataxia telangiectasia.
These neurological features resemble those of ataxia-telangiectasia (AT), but in AOA there are none of the extraneurological features of AT, such as immunodeficiency, neoplasia, chromosomal instability, or sensitivity to ionizing radiation.
The results suggest that aprataxin is a nuclear protein with a role in DNA repair reminiscent of the function of the protein defective in ataxia-telangiectasia, but that would cause a phenotype restricted to neurological signs when mutant.
The characteristic pathological findings of EAOH/AOA1 and AT are a severe loss of Purkinje cells, severe myelin pallor of the posterior columns, and moderate neuronal loss in the dorsal root ganglia and anterior horn.
Included in this group are AT, ataxia-telangiectasia-like disorder (ATLD), ataxia with oculomotor apraxia type 1 (AOA 1), ataxia with oculomotor apraxia type 2 (AOA 2), and the recently described AOA3.
We highlight the importance of considering the diagnosis of AOA1 in children with early-onset cerebellar ataxia, once other well-known disorders such as Friedreich's ataxia and ataxia-telangiectasia have been excluded.
Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis.
As a proof of principle Cockayne syndrome, ataxia with oculomotor apraxia 1 (AOA1), spinocerebellar ataxia with axonal neuropathy 1 (SCAN1) and ataxia-telangiectasia have recently been shown to have mitochondrial dysfunction and those diseases showed strong association with mitochondrial disorders.
Several of the recently identified ARCAs, such as AVED, ARSACS, AOA1, AOA2 and MSS, have a prevalence close to AT and should be searched for extensively irrespective of ethnic origins.
Ataxia and oculomotor apraxia are seen in ataxia-telangiectasia, type 1 ataxia with oculomotor apraxia, and type 2 ataxia with oculomotor apraxia; however, only type 1 ataxia with oculomotor apraxia is associated with aprataxin gene mutation.
Ataxia with oculomotor apraxia types 1-3 (AOA1, 2, and 3) result in a neurodegenerative and cellular phenotype similar to AT; however, the basis of this phenotypic similarity is unclear.