Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.2 (endonuclease)
 18,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In HbSC disease, as in sickle cell anaemia, there is a spectrum of clinical severity. A reduced mean corpuscular volume and haemoglobin concentration, traits typical of thalassaemia, might retard sickling. We therefore ascertained the prevalence of alpha-thalassaemia in 53 adults with HbSC disease and related alpha-globin gene deletion to the haematologic and clinical findings. Alpha-globin genotype was identified by restriction endonuclease gene mapping. Indirect ophthalmoscopy and fluorescein angiography were used to document the presence of proliferative retinopathy. Bone necrosis and infarction were determined roentgenographically or by radionuclide scanning. Either heterozygous or homozygous alpha-thalassaemia-2 was present in 26% of patients. There was no relationship between alpha-globin genotype and haematocrit, pain crises, bone lesions, proliferation retinopathy or clinical severity score.
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PMID:The effects of alpha-thalassaemia in HbSC disease. 663 90

We report a Canadian kindred with a novel mutation in the apolipoprotein (apo) A-I gene causing analphalipoproteinemia. The 34-yr-old proband, product of a consanguineous marriage, had bilateral retinopathy, bilateral cataracts, spinocerebellar ataxia, and tendon xanthomata. High density lipoprotein cholesterol (HDL-C) was < 0.1 mM and apoA-I was undetectable. Genomic DNA sequencing of the proband's apoA-I gene identified a nonsense mutation at codon [-2], which we designate as Q[-2]X. This mutation causes a loss of endonuclease digestion sites for both BbvI and Fnu4HI. Genotyping identified four additional homozygotes, four heterozygotes, and two unaffected subjects among the first-degree relatives. Q[-2]X homozygosity causes a selective failure to produce any portion of mature apoA-I, resulting in very low plasma level of HDL. Heterozygosity results in approximately half-normal apoA-I and HDL. Gradient gel electrophoresis and differential electroimmunodiffusion assay revealed that the HDL particles of the homozygotes had peak Stokes diameter of 7.9 nm and contained apoA-II without apoA-I (Lp-AII). Heterozygotes had an additional fraction of HDL3-like particles. Two of the proband's affected sisters had documented premature coronary heart disease. This kindred, the third reported apoA-I gene mutation causing isolated complete apoA-I deficiency, appears to be at significantly increased risk for atherosclerosis.
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PMID:Apolipoprotein A-I Q[-2]X causing isolated apolipoprotein A-I deficiency in a family with analphalipoproteinemia. 828 91

Aldose reductase (ALR2), the first enzyme of the polyol pathway, may plan an important role in the pathogenesis of diabetic microvascular complications. The gene coding for ALR2 has been localized to chromosome 7q35. Using an ALR2 probe in conjunction with the restriction endonuclease Bam-HI, we have investigated the ALR2 locus of 128 patients with type I diabetes. A significant decrease in the frequency of the 8.2 kilobase (kb) Bam-HI ALR2 genotype and 8.2 kb allele was found in patients with nephropathy (nephropaths) compared to those with retinopathy alone (retinopaths) (p < 0.05 and 0.25, respectively). We have previously shown that an RFLP of the T-cell antigen receptor constant beta-chain (TCRBC) locus, which is also localized to chromosome 7q35, is strongly associated with susceptibility to microvascular complications. The 128 patients were genotyped using the restriction endonuclease Bgl-II and a TCRBC probe. The 10/9.2-8.2 kb TCRBC-ALR2 genotype was significantly decreased in the nephropaths compared to the retinopaths (13.7% versus 43.6%, chi 2 = 10.1, p < 0.0025). The 10/9.2 and 9.2/9.2 kb TCRBC-ALR2 haplotypes were increased in the nephropaths compared to the retinopaths (32.5% versus 8.9% chi 2 = 10.9, p < 0.001). These results suggest that chromosome 7q35 harbors a gene(s) that is involved in the pathogenesis of microvascular complications. Interestingly, the gene coding for endothelial nitric oxide synthase has recently been localized to the same chromosomal region as ALR2.
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PMID:Chromosome 7q35 and susceptibility to diabetic microvascular complications. 877 31

Thirteen patients with sickle cell anemia (SS) were found to have two alpha gene deletions with a presumptive genotype of beta(S)/beta(S); -alpha/-alpha. Hematological data showed that this group of patients had elevated Hb A2 level. In order to determine whether the elevation of Hb A2 is typical of SS with a two alpha gene deletion or is due to undiagnosed S-beta(O)-thalassemia with a two alpha gene deletion we looked for the presence or absence of beta(O)-thalassemia by molecular techniques. The latter included reverse dot-blot hybridization to rule out a beta-thalassemia mutation, digestion with CvnI endonuclease followed by Southern blotting and hybridization with a beta genomic probe, and, in selected patients, determination of the synthetic alpha/beta ratio. One of the 13 patients had S-beta(O)-thalassemia with a G-->A mutation at IVS-II-1 indicating that her genotype was beta(S)/beta(O) thalassemia; -alpha/-alpha. The remaining 12 patients were homozygous for the sickle gene, had relatively elevated Hb levels, increased Hb A2 values, and Hb F levels similar to those in patients with SS and four or three alpha genes. At the clinical level, the 12 patients with SS and a two alpha gene deletion had increased prevalence of avascular necrosis, retinopathy, and splenomegaly, but decreased prevalence of leg ulcers and cerebrovascular accidents. Together, the data indicate that SS with a two alpha gene deletion (beta(S)/beta(S); -alpha/-alpha) is a unique subset of patients with SS characterised by distinct hematological and clinical features.
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PMID:Is Hb A2 elevated in adults with sickle-alpha-thalassemia (beta(S)/beta(S); -alpha/-alpha)? 932 76

Angiogenesis, in which vascular endothelial growth factor receptor (VEGFR) 2 plays an essential role, is associated with a variety of human diseases including proliferative diabetic retinopathy and wet age-related macular degeneration. Here we report that a system of adeno-associated virus (AAV)-mediated clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease (Cas)9 from Streptococcus pyogenes (SpCas9) is used to deplete VEGFR2 in vascular endothelial cells (ECs), whereby the expression of SpCas9 is driven by an endothelial-specific promoter of intercellular adhesion molecule 2. We further show that recombinant AAV serotype 1 (rAAV1) transduces ECs of pathologic vessels, and that editing of genomic VEGFR2 locus using rAAV1-mediated CRISPR/Cas9 abrogates angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization. This work establishes a strong foundation for genome editing as a strategy to treat angiogenesis-associated diseases.Abnormal angiogenesis causes many ocular diseases. Here the authors employ CRISPR/Cas9 gene editing technology to silence VEGFR2, a major regulator of angiogenesis, in retinal endothelium and abrogate angiogenesis in the mouse models of oxygen-induced retinopathy and laser-induced choroid neovascularization.
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PMID:Genome editing abrogates angiogenesis in vivo. 2874 73