Werner’s Syndrome: A Review of its Symptomatology, Natural History, Pathologic Features, Genetics and Relationship to the Natural Aging Process

Epstein, Charles J.; Martin, George M.; Schultz, Amelia L.; Motulsky, Arno G.

doi:10.1007/978-1-4684-7853-2_3

Cited by 274 publications

(436 citation statements)

References 48 publications

Supporting

Mentioning

418

Contrasting

Unclassified

Order By: Relevance

“…Mesenchymal or mesodermally derived cell lineages are preferentially affected by the loss of Wrn (Epstein et al, 1966) and mature adipocytes are derived from a defined mesenchymal pool of pre-adipocytes (Gregoire et al, 1998). We speculate that the metabolic phenotype observed in Wrn null mice is driven by a defect in adipocytes.…”

Section: Discussionmentioning

confidence: 87%

“…Patients can survive up to their fourth or fifth decade of life, but then die of cancer or atherosclerotic cardiovascular disease (or microvascular complications associated with diabetes) (Epstein et al, 1966;Goto, 1997;Huang et al, 2006;Uhrhammer et al, 2006). Diabetes is thought to develop in WS patients due to decreased insulin signaling in tissues that respond to insulin, e.g.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet

Moore

Knoblaugh

Gollahon

et al. 2008

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

Werner syndrome (WS) is an autosomal recessive progeroid syndrome caused by mutations in the Werner gene (Wrn). WS patients have increased incidence of a number of chronic conditions including insulin resistance and type 2 diabetes. Since ingestion of foods that are high in fat and sugar is associated with increased incidence of diabetes, we examined if Wrn mutations might affect metabolic response to a diabetogenic diet. Four month old mice with a null mutation for the Wrn gene were fed a diet consisting of 36% fat (lard), 33% table sugar, and 20% protein plus balanced vitamins and minerals. Wrn null mice had significantly increased body weights, increased serum insulin levels, impaired glucose tolerance, and insulin resistance during four months of eating the diabetogenic diet. Diffuse fatty infiltration of the liver and pancreatic islet hyperplasia were characteristic morphological features. These observations suggest that Wrn null mice have impaired glucose homeostasis and fat metabolism, and may be a useful model to investigate metabolic conditions associated with aging.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet

Moore

Knoblaugh

Gollahon

et al. 2008

Mechanisms of Ageing and Development

View full text Add to dashboard Cite

show abstract

“…Median lifespan of the patients is 54 years, 3 7 years older than in the report in 1966. 14 Similarly, the median lifespan of Japanese…”

Section: Negative Clinical Predictive Value (Probability Not To Develmentioning

confidence: 99%

Clinical utility gene card for: Werner Syndrome - Update 2014

et al. 2014

View full text Add to dashboard Cite

“…Linkage analysis was performed using the computer program LINKAGE version 5.1 (Lathrop et al, 1984). It was assumed that the gene frequency of WRN was 0.004 and the disease was inherited in an autosomal recessive fashion with complete penetrance (Epstein et aL, 1966). A1Me frequency of three microsatellites for lod score calculation was from 50 Japanese controls.…”

Section: Subjects and Diagnosismentioning

confidence: 99%

“…The diagnosis of WS is usually made in the third decade. Skin fibroblasts from WS patients demonstrate slow growth and reduced life span in vitro (Epstein et al, 1966). Recently the WRN locus was mapped to 8pl 1.2-p12, and several microsatellite markers such as ANK1, D8S87, and D8S339 were reported to be closely linked to the WRN locus (Goto et aL, 1992;Schellenberg et aL, 1992;Thomas et al, 1993;Yu et aI., 1994).…”

Section: Introductionmentioning

confidence: 99%

Carrier detection of Werner's syndrome using a microsatellite that exhibits linkage disequilibrium with the Werner's syndrome locus

Kihara

Nakura

et al. 1994

Jap J Human Genet

View full text Add to dashboard Cite

SummaryWerner's syndrome (WS) is a rare autosomal recessive disorder, one of the progeroid syndromes, characterized by features of premature aging. The genetic defect in WS is unknown but recently the genetic linkage of WS to several markers on the short arm of chromosome 8 has been reported. Genetic analysis of 25 families with WS demonstrated that D8S339 was the closest marker linked to the gene locus for Werner's syndrome (WRN), with a peak lod score of 18.29 at recombination frequency 0.001, and showed a linkage disequilibrium with the WRN locus. We studied two unrelated families with WS using ANK1, D8S-339, and D8S360. The mutative haplotype identified through the generations in pedigrees provides a means of carrier detection and presymptomatic diagnosis.

show abstract

Werner’s Syndrome: A Review of its Symptomatology, Natural History, Pathologic Features, Genetics and Relationship to the Natural Aging Process

Cited by 274 publications

References 48 publications

Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet

Hyperinsulinemia and insulin resistance in Wrn null mice fed a diabetogenic diet

Clinical utility gene card for: Werner Syndrome - Update 2014

Carrier detection of Werner's syndrome using a microsatellite that exhibits linkage disequilibrium with the Werner's syndrome locus

Contact Info

Product

Resources

About