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Werner syndrome (WS), also known as adult progeria, is a premature aging syndrome that can manifest itself with gray hair, hair loss, diabetes mellitus, hyperlipidemia, hypertension, skin disorders, ocular cataracts, myocardial infarction, osteoporosis, and stroke, especially after puberty. Physical examination findings similar to systemic sclerosis may be seen. Therefore, it may mimic this disease as misleading. A 43 year-old female patient was admitted to our clinic with a prediagnosis of systemic sclerosis complaint of skin hardening up to the ankle. In the first physical examination, there were wrinkles and thinning of the lip, suggesting systemic sclerosis in the facial appearance. On her capillaroscopy, there was tortuosity and an old focus of microhemorrhage. She had a history of diabetes mellitus and chronic osteomyelitis. When all symptoms, clinical findings, and antibody results were combined, it was thought that the patient might have Werner syndrome. Werner Syndrome was diagnosed with homozygous c.2221 C > P p.R741*(rs763089663) positive in genetic analysis. It is known that Werner syndrome creates a predisposition to malignancies, and most patients die secondary to malignancies. Therefore, early diagnosis becomes essential. Early diagnosis is of vital importance both to prevent complications and to delay treatment. Especially, systemic sclerosis-like findings of this syndrome may cause delays in diagnosis. For this reason, small clues suggesting Werner syndrome in the clinic should be well known and well defined.
Werner syndrome (WS), also known as adult progeria, is a premature aging syndrome that can manifest itself with gray hair, hair loss, diabetes mellitus, hyperlipidemia, hypertension, skin disorders, ocular cataracts, myocardial infarction, osteoporosis, and stroke, especially after puberty. Physical examination findings similar to systemic sclerosis may be seen. Therefore, it may mimic this disease as misleading. A 43 year-old female patient was admitted to our clinic with a prediagnosis of systemic sclerosis complaint of skin hardening up to the ankle. In the first physical examination, there were wrinkles and thinning of the lip, suggesting systemic sclerosis in the facial appearance. On her capillaroscopy, there was tortuosity and an old focus of microhemorrhage. She had a history of diabetes mellitus and chronic osteomyelitis. When all symptoms, clinical findings, and antibody results were combined, it was thought that the patient might have Werner syndrome. Werner Syndrome was diagnosed with homozygous c.2221 C > P p.R741*(rs763089663) positive in genetic analysis. It is known that Werner syndrome creates a predisposition to malignancies, and most patients die secondary to malignancies. Therefore, early diagnosis becomes essential. Early diagnosis is of vital importance both to prevent complications and to delay treatment. Especially, systemic sclerosis-like findings of this syndrome may cause delays in diagnosis. For this reason, small clues suggesting Werner syndrome in the clinic should be well known and well defined.
Werner syndrome (WS), also known as adult progeria, is a rare autosomal recessive inherited progeroid syndrome characterised by multiple features consistent with accelerated ageing. This disease is associated with several rheumatic conditions such as early osteoarthritis and osteoporosis, sarcopenia, soft-tissue calcifications, gout, limb ulcers and scleroderma-like skin features. WS should be included in the differential diagnosis of systemic sclerosis. The diagnosis is clinical, and in 90% of cases, a genetic test reveals a pathogenic variant of the WRN gene.WRN encodes a member of the RecQ family of DNA helicases and has a role in DNA repair. 86 different pathological WRN mutations have been identified so far. Here we present a case report of a typical WS patient associated with a newly described genetic variant of the WRN gene.
The organization of eukaryotic genome in the nucleus, a double-membraned organelle separated from the cytoplasm, is highly complex and dynamic. The functional architecture of the nucleus is confined by the layers of internal and cytoplasmic elements, including chromatin organization, nuclear envelope associated proteome and transport, nuclear–cytoskeletal contacts, and the mechano-regulatory signaling cascades. The size and morphology of the nucleus could impose a significant impact on nuclear mechanics, chromatin organization, gene expression, cell functionality and disease development. The maintenance of nuclear organization during genetic or physical perturbation is crucial for the viability and lifespan of the cell. Abnormal nuclear envelope morphologies, such as invagination and blebbing, have functional implications in several human disorders, including cancer, accelerated aging, thyroid disorders, and different types of neuro-muscular diseases. Despite the evident interplay between nuclear structure and nuclear function, our knowledge about the underlying molecular mechanisms for regulation of nuclear morphology and cell functionality during health and illness is rather poor. This review highlights the essential nuclear, cellular, and extracellular components that govern the organization of nuclei and functional consequences associated with nuclear morphometric aberrations. Finally, we discuss the recent developments with diagnostic and therapeutic implications targeting nuclear morphology in health and disease.
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