Werner syndrome

Werner syndrome
Classification and external resources
ICD-10 E34.8 (ILDS E34.820)
ICD-9 259.8
OMIM 277700
DiseasesDB 14096
MeSH C16.320.925

Werner syndrome (WS, also known as "adult progeria"[1]:573) is a very rare, autosomal recessive[2] disorder characterized by the appearance of premature aging.[3]

Werner syndrome more closely resembles accelerated aging than any other segmental progeria, so it is often referred to as a progeroid syndrome, as it partly mimics the symptoms of progeria.

Contents

History

Werner syndrome is named after Otto Werner,[4] a German scientist, who, as a student, described the syndrome as part of his doctoral thesis in 1904.

Genetics

Werner syndrome is an autosomal recessive disorder.[2] The WRN gene associated with Werner Syndrome lies on chromosome 8 in humans[5] and it is the only gene known to be associated with Werner syndrome.[6] The disease is caused by a mutation in the WRN gene,[6] (or RECQL2) which codes a DNA helicase that functions 3' \to 5' as well as base exertion properties that also function in the same direction. Increased telomere attrition and genomic instability have been observed in Werner syndrome, and rapid telomere decay is thought to play a causal role in the clinical and pathological manifestations of the disease. The process by which the mutant WRN gene promotes telomere instability is unknown.

Onset

Although the symptoms manifest after 10 years, the earliest person diagnosed was six years old.[6] Following puberty, they age rapidly, so that by age 40, they often appear several decades older.

Symptoms

The signs of Werner syndrome are: lack of teenage growth spurt, graying of hair, hoarseness of the voice, thickening of the skin, diabetes mellitus, cataracts, hypogonadism, cancer, and atherosclerosis.[6] Werner causes a "bird-like" pinch to the nose.[6]

Death

In people with Werner syndrome, death usually occurs by myocardial infarction or cancer[6]

Treatment

In 2010, vitamin C supplementation was found to reverse the premature aging and several tissue dysfunctions in a genetically modified mouse model of the disease. Vitamin C supplementation also appeared to normalize several age-related molecular markers such as the increased levels of the transcription factor NF-κB. Vitamin C decreases activity of genes activated in human Werner syndrome, and increases gene activity involved in tissue repair.[7] Vitamin C supplementation is suspected to be beneficial in the treatment of human Werner syndrome, although there was no evidence of anti-aging activity in nonmutant mice.[7]

Popular culture

On the episode "Stargazer in a Puddle" from the series Bones, the victim had Werner syndrome.

Werner syndrome was featured in the film Jack, starring Robin Williams, in which his character aged four times faster than normal.

In one of the earliest cut scenes in the game Metal Gear Solid 4 Hal "Otacon" Emmerich cites "classic Werner syndrome" as the most likely cause of Solid Snake's premature aging.

In season 3 episode 9, " The Ballad of Kevin and Tess", of TV show The 4400, Kevin is said to have Werner syndrome to hide his real condition from the public.

See also

References

  1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
  2. ^ a b Ozgenc A, Loeb LA (Sep 2005). "Current advances in unraveling the function of the Werner syndrome protein". Mutation research 577 (1–2): 237–51. doi:10.1016/j.mrfmmm.2005.03.020. PMID 15946710. 
  3. ^ Gray MD, Shen JC, Kamath-Loeb AS, Blank A, Sopher BL, Martin GM, Oshima J, Loeb LA (Sep 1997). "The Werner syndrome protein is a DNA helicase". Nature genetics 17 (1): 100–3. doi:10.1038/ng0997-100. PMID 9288107. 
  4. ^ synd/892 at Who Named It?
  5. ^ Goto M, Rubenstein M, Weber J, Woods K, Drayna D (Feb 1992). "Genetic linkage of Werner's syndrome to five markers on chromosome 8". Nature 355 (6362): 735–8. doi:10.1038/355735a0. PMID 1741060. 
  6. ^ a b c d e f Leistritz, F. NCBI. Werner Syndrome. Retrieved Jun 2, 2011, from http://www.ncbi.nlm.nih.gov/books/NBK1514/
  7. ^ a b Massip, L.; Garand, C.; Paquet, E. R.; Cogger, V. C.; O'Reilly, J. N.; Tworek, L.; Hatherell, A.; Taylor, C. G.; Thorin, E.; Zahradka, P.; Le Couteur, D. G.; Lebel, M. (2009-09-09). "Vitamin C restores healthy aging in a mouse model for Werner syndrome". The FASEB Journal 24 (1): 158–172. doi:10.1096/fj.09-137133. http://www.fasebj.org/content/24/1/158.short. Retrieved 2011-10-24. 

External links

This article incorporates public domain text from The U.S. National Library of Medicine

DNA replication
DNA repair
Other
see also DNA replication, DNA repair
B structural (perx, skel, cili, mito, nucl, sclr) · DNA/RNA/protein synthesis (drep, trfc, tscr, tltn) · membrane (icha, slcr, atpa, abct, othr) · transduction (iter, csrc, itra), trfk