Varicella-Zoster Virus Is Strongly Associated with Atypical Necrotizing Herpetic Retinopathies

Aqueous humor samples from nine patients with atypical necrotizing retinopathies of suspected viral origin, six with acute retinal necrosis syndrome (ARN), and 17 with active cytomegalovirus (CMV) retinitis underwent amplification for viral DNA of herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and human CMV. VZV DNA was detected in seven of the nine aqueous humor samples from patients with atypical necrotizing retinopathies of suspected viral origin and in four of the six samples from individuals with ARN; of the two other samples from patients with ARNS, no viral DNA was found in one, and both CMV DNA and HSV-1 DNA, but not VZV DNA, were detected in one (this patient presented with bilateral ARNS 2 months after being successfully treated for CMV retinitis). Thus, VZV is likely to be the main pathogen of atypical necrotizing herpetic retinopathies. DNA amplification may be used to establish an early, sensitive, and reliable diagnosis of any form of necrotizing retinopathy in 80% of cases, irrespective of viral etiolog

Varicella-Zoster Virus Is Strongly Associated with Atypical Necrotizing Herpetic Retinopathies

Aqueous humor samples from nine patients with atypical necrotizing retinopathies of suspected viral origin, six with acute retinal necrosis syndrome (ARN), and 17 with active cytomegalovirus (CMV) retinitis underwent amplification for viral DNA of herpes simplex virus type 1 (HSV-1), varicella-zoster virus (VZV), and human CMV. VZV DNA was detected in seven of the nine aqueous humor samples from patients with atypical necrotizing retinopathies of suspected viral origin and in four of the six samples from individuals with ARN; of the two other samples from patients with ARNS, no viral DNA was found in one, and both CMV DNA and HSV-1 DNA, but not VZV DNA, were detected in one (this patient presented with bilateral ARNS 2 months after being successfully treated for CMV retinitis). Thus, VZV is likely to be the main pathogen of atypical necrotizing herpetic retinopathies. DNA amplification may be used to establish an early, sensitive, and reliable diagnosis of any form of necrotizing retinopathy in 80% of cases, irrespective of viral etiology

Altered tumor formation and evolutionary selection of genetic variants in the human MDM4 oncogene

A large body of evidence strongly suggests that the p53 tumor suppressor pathway is central in reducing cancer frequency in vertebrates. The protein product of the haploinsufficient mouse double minute 2 (MDM2) oncogene binds to and inhibits the p53 protein. Recent studies of human genetic variants in p53 and MDM2 have shown that single nucleotide polymorphisms (SNPs) can affect p53 signaling, confer cancer risk, and suggest that the pathway is under evolutionary selective pressure (1–4). In this report, we analyze the haplotype structure of MDM4, a structural homolog of MDM2, in several different human populations. Unusual patterns of linkage disequilibrium (LD) in the haplotype distribution of MDM4 indicate the presence of candidate SNPs that may also modify the efficacy of the p53 pathway. Association studies in 5 different patient populations reveal that these SNPs in MDM4 confer an increased risk for, or early onset of, human breast and ovarian cancers in Ashkenazi Jewish and European cohorts, respectively. This report not only implicates MDM4 as a key regulator of tumorigenesis in the human breast and ovary, but also exploits for the first time evolutionary driven linkage disequilibrium as a means to select SNPs of p53 pathway genes that might be clinically relevant