HOME

TheInfoList



OR:

Werner syndrome (WS) or Werner's syndrome, also known as "adult progeria",James, William; Berger, Timothy; Elston, Dirk (2005). ''Andrews' Diseases of the Skin: Clinical Dermatology''. (10th ed.). Saunders. . is a rare, autosomal recessive disorder which is characterized by the appearance of premature aging. Werner syndrome is named after the German scientist
Otto Werner Carl Wilhelm Otto Werner (1 February 1879 – 5 June 1936) was a German physician, after whom Werner syndrome, a form of progeria, was named. As a medical student in 1903, Werner observed the syndrome in four siblings near the age of 30. He documen ...
. He identified the syndrome in four siblings observed with premature aging, which he explored as the subject of his dissertation of 1904. It has a global incidence rate of less than 1 in 100,000 live births (although incidence in Japan and Sardinia is higher, affecting 1 in 20,000–40,000 and 1 in 50,000, respectively). 1,300 cases had been reported as of 2006. Affected individuals typically grow and develop normally until puberty; the mean age of diagnosis is twenty-four, often realized when the adolescent growth spurt is not observed. The youngest person diagnosed was six years old. The median and mean ages of death are 47–48 and 54 years, respectively.Oshima J, Martin GM, Hisama FM. Werner Syndrome. 2002 Dec 2 pdated 2012 Dec 13 In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews nternet Seattle (WA): University of Washington, Seattle; 1993-. Available from:https://www.ncbi.nlm.nih.gov/books/NBK1514/ The main causes of death are
cardiovascular disease Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, ...
and cancer.


Presentation

Werner syndrome patients exhibit growth retardation, short stature, premature graying of hair, alopecia (hair loss),
wrinkling A wrinkle, also known as a rhytid, is a fold, ridge or crease in an otherwise smooth surface, such as on skin or fabric. Skin wrinkles typically appear as a result of ageing processes such as glycation, habitual sleeping positions, loss of bo ...
, prematurely aged faces with beaked noses, skin
atrophy Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include mutations (which can destroy the gene to build up the organ), poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply ...
(wasting away) with scleroderma-like
lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classif ...
s, lipodystrophy (loss of fat tissues), abnormal fat deposition leading to thin legs and arms, and severe ulcerations around the Achilles tendon and malleoli (around ankles). Other symptoms include change in voice (weak, hoarse, high-pitched), atrophy of gonads leading to reduced
fertility Fertility is the capability to produce offspring through reproduction following the onset of sexual maturity. The fertility rate is the average number of children born by a female during her lifetime and is quantified demographically. Ferti ...
, bilateral cataracts (clouding of lens), premature arteriosclerosis (thickening and loss of elasticity of arteries), calcinosis (calcium deposits in blood vessels),
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually ...
(blockage of blood vessels),
type 2 diabetes Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urinati ...
, osteoporosis (loss of bone mass), telangiectasia, and malignancies. The prevalence of rare cancers, such as meningiomas, are increased in individuals with Werner syndrome.


Gene expression

Gene transcription changes found in WS cells are strikingly similar to those observed in normal aging. At the level of gene expression, WRN protein deficiency causes changes in the pattern of
gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. ...
that markedly resemble those of normal old age.


DNA methylation

The blood of WS patients exhibits accelerated DNA methylation changes that are similar to those observed in normal aging according to a molecular biomarker of aging known as epigenetic clock.


Diagnosis and clinical symptoms

The mutation in the WRN gene that causes Werner syndrome is autosomal and recessive, meaning that sufferers must inherit a copy of the gene from each parent. Patients display rapid premature aging beginning in young adulthood, usually in their early twenties. Diagnosis is based on six cardinal symptoms: premature graying of the hair or hair loss, presence of bilateral cataracts, atrophied or tight skin, soft tissue calcification, sharp facial features, and an abnormal, high-pitched voice. Patients are generally short-statured due to absence of the adolescent growth spurt. Patients also display decreased fertility. The most common symptom of the six is premature graying and loss of hair. This is also generally the earliest observed symptom, with hair loss occurring first on the scalp and the eyebrows. Werner syndrome patients often have skin that appears shiny and tight, and may also be thin or hardened. This is due to atrophy of the subcutaneous tissue and dermal fibrosis. Over time, the characteristic facial features may be more apparent due to these skin conditions. Other associated skin conditions include ulcers, which are very difficult to treat in Werner syndrome patients, and are caused in part by decreased potential of skin cells for replication. WS cataracts are distinctly different from those of normal aging. They are associated with problems in the
lens A lens is a transmissive optical device which focuses or disperses a light beam by means of refraction. A simple lens consists of a single piece of transparent material, while a compound lens consists of several simple lenses (''elements'' ...
posterior cortex and subcapsular regions. These cataracts are generally treatable with cataract surgery, which should restore normal vision. Symptoms become apparent in the late teens and early twenties and continue to progress. Most patients live to about fifty years of age. The most common causes of death for people are associated diseases and complications, especially atherosclerosis and cancer.


Associated diseases

Werner syndrome patients are at increased risk for several other diseases, many associated with aging.
Atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually ...
, the thickening of artery walls due to cholesterol buildup, is one common complication. While normal atherosclerosis generally involves the major arteries, smaller arterioles are more likely to be affected. It is possible nervous system disorders are associated. Brain atrophy is present in 40% of patients. Osteoporosis, the loss of bone mineral density common in post-menopausal women, is another common symptom. In contrast with the normal population, the rate of osteoporosis is especially high for male patients.
Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...
is another common accompaniment. Skin ulcers occur in about 75% of patients – and can be difficult to treat. If skin ulcers become badly infected or develop gangrene, they often require
amputation Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on ind ...
. Unlike most other related diseases and complications, these ulcers are not associated with normal aging. Patients are also at an increased risk of cancer, especially malignant melanoma. Soft-tissue sarcomas are the most common cancer types. Other types of skin cancer, other epithelial cancers such as thyroid and
liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
cancers, MDS ( myelodysplastic syndrome), and MFH ( malignant fibrous histiocytoma) are also prevalent among. Mutations in the WRN gene, especially single-nucleotide polymorphisms (SNPs), are associated with many of the cancers and other associated diseases. WRN SNPs correlate with cancers such as sarcomas and non-Hodgkin lymphomas, as well as diabetes and cardiovascular problems including atherosclerosis.


Causes

Approximately 90% of individuals presenting Werner syndrome have any of a range of mutations in the gene, '' WRN'', the only gene currently attributed to cause Werner syndrome. ''WRN'', which lies on chromosome 8 in humans, encodes the WRNp protein, a 1432 amino acid protein with a central domain resembling members of the RecQ helicases. RecQ helicases are a special type of helicase that function at unique times during DNA repair of doubled stranded breaks, which are a form of
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
that results in a break of both strands of DNA. Thus, RecQ helicases are important for maintaining DNA stability, and loss of function of these helicases has important implications in the development of Werner syndrome. In addition to the central domain, there are three exonuclease domains at the
N-terminus The N-terminus (also known as the amino-terminus, NH2-terminus, N-terminal end or amine-terminus) is the start of a protein or polypeptide, referring to the free amine group (-NH2) located at the end of a polypeptide. Within a peptide, the ami ...
and a Helicase and Ribonuclease D C-terminal (HRDC) domain at the
C-terminus The C-terminus (also known as the carboxyl-terminus, carboxy-terminus, C-terminal tail, C-terminal end, or COOH-terminus) is the end of an amino acid chain (protein or polypeptide), terminated by a free carboxyl group (-COOH). When the protein i ...
. When functioning normally, the ''WRN'' gene and its associated protein (WRNp) are important for maintaining genome stability. WRNp is active in unwinding DNA, a step necessary in DNA repair and
DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all living organisms acting as the most essential part for biological inherita ...
. Specifically, it has an important role in responding to replication malfunctions, particularly double-stranded breaks, and stalled replication machinery. WRNp may reactivate replication by preventing unwanted recombination processes from occurring or by promoting recombination, depending on the type of DNA damage. In addition, WRNp physically interacts with or binds to several other proteins that are involved in processing DNA. For example, when WRNp binds to RPA, its helicase activity is stimulated. WRNp also physically interacts with p53, a tumor suppressor gene that stops the formation of tumors and the progression of cancers, which inhibits the exonuclease activity of the WRNp. Since WRNp's function depends on DNA, it is only functional when localized to the nucleus. Surprisingly, complete loss of WRN helicase activity does not cause clinical Werner syndrome.


DNA repair processes

The finding that WRN protein interacts with DNA-PKcs and the
Ku protein Ku is a dimeric protein complex that binds to DNA double-strand break ends and is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Ku is evolutionarily conserved from bacteria to humans. The ancestral bacterial Ku i ...
complex, combined with evidence that WRN deficient cells produce extensive deletions at sites of joining of non-homologous DNA ends, suggests a role for WRN protein in the DNA repair process of
non-homologous end joining Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks in DNA. NHEJ is referred to as "non-homologous" because the break ends are directly ligated without the need for a homologous template, in contrast to homology direct ...
(NHEJ). WRN protein also physically interacts with the major NHEJ factor X4L4 ( XRCC4- DNA ligase 4 complex). X4L4 stimulates WRN exonuclease activity that likely facilitates DNA end processing prior to final ligation by X4L4. WRN protein appears to play a role in resolving recombination intermediate structures during
homologous recombination Homologous recombination is a type of genetic recombination in which genetic information is exchanged between two similar or identical molecules of double-stranded or single-stranded nucleic acids (usually DNA as in cellular organisms but may be ...
al repair (HRR) of DNA double-strand breaks. WRN protein participates in a complex with RAD51, RAD54,
RAD54B DNA repair and recombination protein RAD54B is a protein that in humans is encoded by the ''RAD54B'' gene. The protein encoded by this gene belongs to the DEAD-like helicase superfamily. It shares similarity with ''Saccharomyces cerevisiae'' RAD5 ...
and ATR proteins in carrying out the recombination step during inter-strand DNA cross-link repair. Evidence was presented that WRN protein plays a direct role in the repair of methylation induced
DNA damage DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA da ...
. This process likely involves the
helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separat ...
and
exonuclease Exonucleases are enzymes that work by cleaving nucleotides one at a time from the end (exo) of a polynucleotide chain. A hydrolyzing reaction that breaks phosphodiester bonds at either the 3′ or the 5′ end occurs. Its close relative is t ...
activities of WRN protein that operate together with
DNA polymerase beta DNA polymerase beta, also known as POLB, is an enzyme present in eukaryotes. In humans, it is encoded by the ''POLB'' gene. Function In eukaryotic cells, DNA polymerase beta (POLB) performs base excision repair (BER) required for DNA maint ...
in long patch
base excision repair Base excision repair (BER) is a cellular mechanism, studied in the fields of biochemistry and genetics, that repairs damaged DNA throughout the cell cycle. It is responsible primarily for removing small, non-helix-distorting base lesions from t ...
.


Effects on cell structure and function

Mutations which cause Werner syndrome all occur at the regions of the gene which encode for protein, and not at non-coding regions. There are 35 different known mutations of WRN, which correspond to
stop codons In molecular biology (specifically protein biosynthesis), a stop codon (or termination codon) is a codon (nucleotide triplet within messenger RNA) that signals the termination of the translation process of the current protein. Most codons in mess ...
, insertions, or deletions that result in a
frameshift Ribosomal frameshifting, also known as translational frameshifting or translational recoding, is a biological phenomenon that occurs during translation that results in the production of multiple, unique proteins from a single mRNA. The process c ...
mutation. These mutations can have a range of effects. They may decrease the stability of the transcribed messenger RNA (mRNA), which increases the rate at which they are degraded. With less mRNA, less is available to be translated into the WRNp protein. Mutations may also lead to the truncation (shortening) of the WRNp protein, leading to the loss of its nuclear localization signal sequence, thus it is no longer transported into the nucleus where it interacts with the DNA. This leads to a reduction in DNA repair. Furthermore, mutated proteins are more likely to be degraded than normal WRNp. Apart from causing defects in DNA repair, its aberrant association with p53 down-regulates the function of p53, leading to a reduction in p53-dependent apoptosis and increasing the survival of these dysfunctional cells. Cells of affected individuals also have reduced lifespan in
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and norms found in human societies, as well as the knowledge, beliefs, arts, laws, customs, capabilities, and habits of the individuals in these grou ...
, have more chromosome breaks and translocations and have extensive deletions. Patients with Werner syndrome lose the RecQ helicase activity in the WRN protein because of the loss of its C-terminus region, but the mechanism by which this happens is unclear. The loss of the helicase activity can have far-reaching consequences in terms of cell stability and mutation. One instance of these consequences involves telomeres. It is thought that the WRN helicase activity is important not only for DNA repair and recombination, but also for maintaining telomere length and stability. Thus, WRN helicase is important for preventing catastrophic telomere loss during DNA replication. In a normal cell, the telomeres (the ends of chromosomes) undergo repeated shortening during the
cell cycle The cell cycle, or cell-division cycle, is the series of events that take place in a cell that cause it to divide into two daughter cells. These events include the duplication of its DNA ( DNA replication) and some of its organelles, and sub ...
, which can prevent the cell from dividing and multiplying. This event can be counteracted by
telomerase Telomerase, also called terminal transferase, is a ribonucleoprotein that adds a species-dependent telomere repeat sequence to the 3' end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most e ...
, an enzyme that extends the ends of the chromosomes by copying the telomeres and synthesizing an identical, but new end that can be added to the existing chromosome. However, patients with Werner syndrome often exhibit accelerated telomere shortening, indicating that there may be a connection between the loss of the WRN helicase activity and telomere and cell instability. While evidence shows that telomere dysfunction is consistent with the premature aging in WS, it has yet to be determined if it is the actual cause of the genomic instability observed in cells and the high rate of cancer in WS patients. Without the WRN protein, the interwoven pathways of DNA repair and telomere maintenance fail to suppress cancer and the aging symptoms seen in patients with WS. Events such as rapid telomere shortening cause Werner syndrome cells to exhibit low responses to overall cellular stress. In addition to telomere dysfunction, over-expression of oncogenes and
oxidation Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...
can induce this type of response. High stress causes a synergistic effect, where WS cells become even more sensitive to agents that increase cell stress and agents that damage DNA. As a result, WS cells show a drastic reduction in replicative lifespan and enter into a stage of aging prematurely. The accumulation of these damaged cells due to telomere shortening over many years may be indicative of why Werner syndrome symptoms only appear after an individual is about twenty years old.


Protection of DNA against oxidative damage

WRN protein was found to have a specific role in preventing or repairing DNA damages resulting from chronic
oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal re ...
, particularly in slowly replicating cells. This finding suggested that WRN may be important in dealing with oxidative DNA damage that underlies normal aging (see DNA damage theory of aging).


Diagnosis


Treatment

A cure for Werner syndrome has not yet been discovered. It is often treated by managing the associated diseases and relieving symptoms to improve quality of life. The skin ulcers that accompany WS can be treated in several ways, depending on the severity. Topical treatments can be used for minor ulcers, but are not effective in preventing new ulcers from occurring. In the most severe cases, surgery may be required to implant a skin graft or amputate a limb if necessary. Diseases commonly associated with Werner syndrome such as diabetes and cancer are treated in generally the same ways as they would be for a non-Werner syndrome individual. A change in diet and exercise can help prevent and control arteriosclerosis, and regular cancer screenings can allow for early detection of cancer. There is evidence that suggests that the
cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in a ...
-suppressive anti-inflammatory drug
SB203580 SB 203580 is a specific inhibitor of p38α and p38β which suppresses downstream activation of MAPKAP kinase-2 and heat shock protein 27. At low concentrations, it does not inhibit JNK c-Jun N-terminal kinases (JNKs), were originally iden ...
may be a possible therapeutic option for patients with Werner's syndrome. This drug targets the p38 signaling pathway, which may become activated as a result of genomic instability and stalled replication forks that are characteristic mutations in WS. This activation of p38 may play a role in the onset of premature cell aging, skin aging, cataracts, and graying of the hair. The p38 pathway has also been implicated in the inflammatory response that causes atherosclerosis, diabetes, and osteoporosis, all of which are associated with Werner's syndrome. This drug has shown to revert the aged characteristics of young WS cells to those seen in normal, young cells and improve the lifespan of WS cells ''in vitro''. SB203580 is in the clinical trial stages, and the same results have not yet been seen ''in vivo''. In 2010,
vitamin C Vitamin C (also known as ascorbic acid and ascorbate) is a water-soluble vitamin found in citrus and other fruits and vegetables, also sold as a dietary supplement and as a topical 'serum' ingredient to treat melasma (dark pigment spots) a ...
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 Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular ...
. In addition, it decreases activity of genes activated in human Werner syndrome and increases gene activity involved in tissue repair. Supplementation of vitamin C is suspected to be beneficial in the treatment of human Werner syndrome, although there was no evidence of anti-aging activity in nonmutant mice. In general, treatments are available for only the symptoms or complications and not for the disease itself.


History

Otto Werner was the first to observe Werner syndrome in 1904 as a part of his dissertation research. As a German ophthalmologist, Werner described several progeria-like features and juvenile cataracts in many of his patients. He noticed these symptoms particularly in a family with four sequential children who all showed the characteristics of the syndrome at around the same age. He assumed the cause to be genetic, though most of his evidence was clinical. Between 1934 and 1941, two internists from New York, Oppenheimer and Kugel, coined the term "Werner Syndrome," igniting a wave of interest and research on the disease. During that time, Agatson and Gartner suggested a possible link between Werner's syndrome and cancer. However, it was not until 1966 that there was a general consensus on the autosomal recessive mode of inheritance for the syndrome. By 1981, geneticists had located the WRN gene on chromosome 8, leading to its cloning in 1996. This cloning of the WRN was significant because it revealed the predicted WRN protein was made from a family of DNA
helicase Helicases are a class of enzymes thought to be vital to all organisms. Their main function is to unpack an organism's genetic material. Helicases are motor proteins that move directionally along a nucleic acid phosphodiester backbone, separat ...
s. Prior to 1996, Werner syndrome was thought to be a model for accelerated aging. Since the discovery of the gene, it has become clear that the premature aging displayed in Werner syndrome is not the same, on a cellular level, as normal aging. The role of WRN in DNA repair and its exonuclease and helicase activities have been the subject of many studies in recent years. Since the initial discovery in 1904, several other cases of Werner syndrome have been recorded. Many of these cases have occurred in Japan, where a founder effect has caused a higher incidence rate than in other populations. The incidence rate of Werner syndrome in Japan is approximately 1 case per 100 thousand people (1:100,000), a large contrast with the rate of incidence for the rest of the world, which is between 1:1,000,000 and 1:10,000,000. A founder effect is also apparent in Sardinia, where there have been 18 recorded cases of Werner syndrome.


Society and culture

On the episode "Stargazer in a Puddle" from the television series '' Bones'', the victim has Werner syndrome. The team discovers in the course of the investigation that her mother killed her because she was dying of another disease, and worried that her daughter would have nobody to look after her afterwards, with the tragic twist that the mother began to recover from her disease after her daughter's death. Werner syndrome is featured in the 1989 film '' The Fly II'', starring
Eric Stoltz Eric Cameron Stoltz (born September 30, 1961) is an American actor, director and producer. He played the role of Rocky Dennis in the biographical drama film ''Mask'', which earned him the nomination for the Golden Globe Award for Best Suppor ...
, in which his character is born as a 2-year-old baby. He never sleeps and grows 5 times his normal age due to his biological father having half fly genes from the first 1986 film '' The Fly''. Werner syndrome is also featured in the 1996 film '' Jack'', starring Robin Williams, in which his character ages four times faster than normal. In an early cutscene from the game '' Metal Gear Solid 4'', Otacon cites "classic Werner syndrome" as the most likely cause of Solid Snake's premature aging, though he goes on to say that testing had been inconclusive. It is however later said that Solid Snake's body, created as a genetically engineered clone, had been designed to break down quickly. In season 3 episode 9, " The Ballad of Kevin and Tess", of the TV series '' The 4400'', Kevin is said to have Werner syndrome to hide his real condition from the public. In '' The Invisible Man'' season 1 episode 6, "Impetus", the new character Gloria has an experimentally altered type of Werner syndrome that causes it to become contagious. The central character in Gail Tsukiyama's novel ''DREAMING WATER'' (2002) has Werner's syndrome. In season 1 episode 8 "Cold Comfort" from TV series '' Dark Angel'', a character has a "form of progeria, similar to Werner syndrome", due to genetic manipulation. With an appropriate treatment, her condition seems to be stabilized. In '' Resident Evil: The Final Chapter'' (2016), the deadly "T-Virus", which causes the viral pandemic in the ''Resident Evil'' film series, is revealed to be the cure for "adult progeria". James Marcus originally develops the virus to cure his young daughter Alicia Marcus. '' Ratsasan'' (2018), a Tamil movie (as well as its Telugu remake '' Rakshasudu''), features a young man born with Werner's and is a victim of childhood bullying due to his appearance and has bad experience proposing to a girl, who turns into serial killer and hunts down and kills school girls. '' Yashoda'' (2022), an Indian movie, portrays the antagonist suffering from Werner and using human foetuses to regain her beauty.


See also


References


External links

''This article incorporates public domain text fro
The U.S. National Library of Medicine
'
Werner Syndrome from GeneReviews
contains extensive information on the disorder {{DEFAULTSORT:Werner Syndrome Genodermatoses Autosomal recessive disorders Rare diseases Syndromes affecting the cardiovascular system DNA replication and repair-deficiency disorders Progeroid syndromes Syndromes affecting stature Syndromes affecting bones Syndromes affecting the nervous system sv:Progeri#Werners syndrom