Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0086543 (cataract)
 29,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Werner syndrome is caused by mutations in the DNA repair Werner helicase (WRN) gene and characterized by accelerated aging including cataracts. Age-related cataract (ARC) cases (N = 504) and controls (N = 244) were recruited from a population-based study to evaluate the association of single-nucleotide polymorphisms (SNPs) of WRN and another DNA repair gene (human 8-oxoguanine DNA N-glycosylase 1) with ARC. Among the five SNPs tested, only WRN rs1346044 was found to be significantly associated between cases and controls before multiple-testing adjustment. The minor C allele of rs1346044 was associated with ARC with an odds ratio (OR) of 0.66, suggesting a protective role of the C allele for developing ARC. The stratification analysis on the subtypes of ARC showed that rs1346044 was significantly associated with cortical cataract, but not with nuclear, posterior subcapsular, and mixed types after multiple-testing adjustment (OR = 0.51, p< 0.01). The genetic model analysis showed that the results fit the dominant model (OR = 0.44, p < 0.001). The comet assay used to assess the extent of DNA damage in peripheral lymphocytes of ARC cases found that the DNA damage in lymphocytes from patients with CC genotype was significantly less than that in patients with TT genotype. We concluded that the C allele of rs1346044, a non-synonymous SNP resulting in the conversion of Cys to Arg at amino acid position 1367 of WRN, alters susceptibility to ARC, especially the cortical type of the disease, in the Han Chinese. The underlying mechanism of its protective role might be related to the improved DNA repair function.
 ...
PMID:Polymorphisms of the WRN gene and DNA damage of peripheral lymphocytes in age-related cataract in a Han Chinese population. 2333 3

Atypical progeroid syndrome (APS), including atypical Werner syndrome (AWS), is a progeroid syndrome involving heterozygous mutations in the LMNA gene encoding the nuclear protein lamin A/C. We report the first Japanese case of APS/AWS with a LMNA mutation (p.D300N). A 53-year-old Japanese man had a history of recurrent severe cardiovascular diseases as well as brain infarction and hemorrhages. Although our APS/AWS patient had overlapping features with Werner syndrome (WS), such as high-pitched voice, scleroderma, lipoatrophy and atherosclerosis, several cardinal features of WS, including short stature, premature graying/alopecia, cataract, bird-like face, flat feet, hyperkeratosis on the soles and diabetes mellitus, were absent. In immunofluorescence staining and electron microscopic analyses of the patient's cultured fibroblasts, abnormal nuclear morphology, an increase in small aggregation of heterochromatin and a decrease in interchromatin granules in nuclei of fibroblasts were observed, suggesting that abnormal nuclear morphology and chromatin disorganization may be associated with the pathogenesis of APS/AWS.
...
PMID:First Japanese case of atypical progeroid syndrome/atypical Werner syndrome with heterozygous LMNA mutation. 2532 15

Purpose. To examine the promoter methylation and histone modification of WRN (Werner syndrome gene), a DNA repair gene, and their relationship with the gene expression in age-related cataract (ARC) lens. Methods. We collected the lenses after cataract surgery from 117ARC patients and 39 age-matched non-ARC. WRN expression, DNA methylation and histone modification around the CpG island were assessed. The methylation status of Human-lens-epithelium cell (HLEB-3) was chemically altered to observe the relationship between methylation and expression of WRN. Results. The WRN expression was significantly decreased in the ARC anterior lens capsules comparing with the control. The CpG island of WRN promoter in the ARC anterior lens capsules displayed hypermethylation comparing with the controls. The WRN promoter was almost fully methylated in the cortex of ARC and control lens. Acetylated H3 was lower while methylated H3-K9 was higher in ARC anterior lens capsules than that of the controls. The expression of WRN in HLEB-3 increased after demethylation of the cells. Conclusions. A hypermethylation in WRN promoter and altered histone modification in anterior lens capsules might contribute to the ARC mechanism. The data suggest an association of altered DNA repair capability in lens with ARC pathogenesis.
...
PMID:Epigenetic Regulation of Werner Syndrome Gene in Age-Related Cataract. 2650 79

Here, we present, to the best of our knowledge, the first case of Werner syndrome with corneal blindness due to bilateral primary bullous keratopathy. Werner syndrome is a rare autosomal recessive disorder characterized by features of premature aging, insulin-dependent diabetes mellitus, osteoporosis, atherosclerosis, hypergonadotrophic hypogonadism, hypertriglyceridemia, scleroderma-like skin changes, and sarcomas. Among ocular manifestations, cataracts, cystoid macular edema, and retinal detachment have been reported. Because these patients show features of premature aging, they have decreased corneal endothelial function and delayed fibroblast growth. To date, there are few reports of wound dehiscence, bleb formation, and bullous keratopathy following surgical insult that have usually occurred after cataract surgery in patients with Werner syndrome. There have been no reports in the literature regarding Werner syndrome presenting with primary corneal decompensation without any inciting factor. Our patient with Werner syndrome had primary bilateral bullous keratopathy and bilateral corneal blindness for 10 years and was eventually rehabilitated by corneal transplant. Hence, this case highlights the importance of early referral of such patients to the ophthalmologist for prompt diagnosis and early treatment so that blindness could be avoided.
 ...
PMID:Primary Bullous Keratopathy in a Patient With Werner Syndrome Treated With Corneal Transplant. 2953 62

Werner syndrome (WS) is a rare progressive disorder. It is characterized by the appearance of unusually accelerated aging (progeria) including bilateral senile cataract. Here, we report a successful management of hypermature cataract in WS.
 ...
PMID:Management of cataract in Werner syndrome. 3012 65

Werner's syndrome (WS) or progeria adultorum is a heritable autosomal recessive disease in which the aging process is accelerated, just after puberty. It is caused by mutations in the WRN gene, which encodes a member of the RECQ family of DNA helicases and has a role in DNA repair. WS is being more appropriately recognized as a condition in which the lack of WRN protein results in an overall decline in the normal physiological functions of various organs rather than premature aging. Here, we describe a rare case of WS with a novel mutation from India. Our patient was an adult male with a history of growth arrest since puberty and other clinical features such as sclerodermatous skin changes, premature graying and thinning of hair, bilateral cataract, a single non-healing ulcer, hypothyroidism, underdeveloped secondary sexual characters with hypogonadism, infertility, squeaky voice, and early signs of arteriosclerosis. On genetic analysis, he was found to have a homozygous pathogenic variant c.3190C>T in exon 26 of the WRN gene, which has never been reported in WS.
 ...
PMID:A Case Report of Werner's Syndrome With a Novel Mutation From India. 3252 64


<< Previous 1 2 3