DNA Repair Enzymes
Transcription Factor TFIIH
Xeroderma Pigmentosum Group D Protein
Nuclear Receptor Subfamily 2, Group C, Member 2
RNA Polymerase II
Skin Diseases, Genetic
Mutant Chimeric Proteins
Xeroderma Pigmentosum Group A Protein
Transcription Factors, TFII
Genetic Complementation Test
Cell Line, Transformed
Metabolic Syndrome X
Base excision repair of oxidative DNA damage activated by XPG protein. (1/194)Oxidized pyrimidines in DNA are removed by a distinct base excision repair pathway initiated by the DNA glycosylase--AP lyase hNth1 in human cells. We have reconstituted this single-residue replacement pathway with recombinant proteins, including the AP endonuclease HAP1/APE, DNA polymerase beta, and DNA ligase III-XRCC1 heterodimer. With these proteins, the nucleotide excision repair enzyme XPG serves as a cofactor for the efficient function of hNth1. XPG protein promotes binding of hNth1 to damaged DNA. The stimulation of hNth1 activity is retained in XPG catalytic site mutants inactive in nucleotide excision repair. The data support the model that development of Cockayne syndrome in XP-G patients is related to inefficient excision of endogenous oxidative DNA damage. (+info)
Alterations in the CSB gene in three Italian patients with the severe form of Cockayne syndrome (CS) but without clinical photosensitivity. (2/194)Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by postnatal growth failure, mental retardation and otherwise clinically heterogeneous features which commonly include cutaneous photosensitivity. Cultured cells from sun-sensitive CS patients are hypersensitive to ultraviolet (UV) light and, following UV irradiation, are unable to restore RNA synthesis rates to normal levels. This has been attributed to a specific deficiency in CS cells in the ability to carry out preferential repair of damage in actively transcribed regions of DNA. We report here a cellular and molecular analysis of three Italian CS patients who were of particular interest because none of them was sun-sensitive, despite showing most of the features of the severe form of CS, including the characteristic cellular sensitivity to UV irradiation. They all were altered in the CSB gene. The genetically related patients CS1PV and CS3PV were homozygous for the C1436T transition resulting in the change Arg453opal. Patient CS2PV was a compound heterozygote for two new causative mutations, insertions of an A at position 1051 and of TGTC at 2053, leading to truncated proteins of 367 and 681 amino acids. These mutations result in severely truncated proteins, as do many of those that we previously identified in several sun-sensitive CS-B patients. These observations confirm that the CSB gene is not essential for viability and cell proliferation, an important issue to be considered in any speculation on the recently proposed additional function of the CSB protein in transcription. Our investigations provide data supporting the notion that other factors, besides the site of the mutation, influence the type and severity of the CS clinical features. (+info)
The relative expression of mutated XPB genes results in xeroderma pigmentosum/Cockayne's syndrome or trichothiodystrophy cellular phenotypes. (3/194)The human XPB DNA helicase is a subunit of the DNA repair/basal transcription factor TFIIH, involved in early steps of the nucleotide excision repair pathway. Two distinct clinical phenotypes, xeroderma pigmentosum associated with Cockayne's syndrome (XP/CS) and trichothiodystrophy (TTD), can be due to mutations in the XPB gene. In the present work, we studied cellular DNA repair properties of skin fibro-blasts from two patients mutated in the XPB gene: an XP/CS patient cell (XPCS2BA) with a T296C (F99S) transition and a TTD patient cell (TTD6VI) exhibiting an A355C (T119P) transversion. Both cells are clearly associated with different levels of alterations in their response to UV light. To establish the relationship between the relative expression level of these two alleles and DNA repair properties, we transfected SV40-transformed XPCS2BA (XPCS2BASV) cells with a plasmid (pTTD6VI) carrying the XPB-A355C cDNA and examined DNA repair properties after UV irradiation (cell survival, unscheduled DNA synthesis and kinetics of photoproduct removal) in stable transfectants. We isolated three clones, which express the XPB-A355C gene (Cl-5) or the XPB-T296C gene (Cl-14) or both genes (Cl-19). This con-stitutes a model system allowing us to correlate the relative expression levels of the XPB-A355C (TTD) and XPB-T296C (XP/CS) genes with various DNA repair properties. Overexpression of the XPB-A355C (TTD) gene in an XP/CS cell gives rise to a cellular phenotype of increased repair similar to that of TTD6VI cells, while equal expression of the two mutated genes leads to an intermediate cellular phenotype between XP/CS and TTD. (+info)
Cells from XP-D and XP-D-CS patients exhibit equally inefficient repair of UV-induced damage in transcribed genes but different capacity to recover UV-inhibited transcription. (4/194)Xeroderma pigmentosum (XP) is a rare hereditary human disorder clinically associated with severe sun sensitivity and predisposition to skin cancer. Some XP patients also show clinical characteristics of Cockayne syndrome (CS), a disorder associated with defective preferential repair of DNA lesions in transcriptionally active genes. Cells from the two XP-patients who belong to complementation group D and exhibit additional clinical symptoms of CS are strikingly more sensitive to the cytotoxic effects of UV-light than cells from classical XP-D patients. To explain the severe UV-sensitivity it was suggested that XP-D-CS cells have a defect in preferential repair of UV-induced 6-4 photoproducts (6-4PP) in active genes. We investigated the capacity of XP-D and XP-D-CS cells to repair UV-induced DNA lesions in the active adenosine deaminase gene (ADA) and in the inactive 754 gene by determining (i) the removal of specific lesions, i.e. cyclobutane pyrimidine dimers (CPD) and 6-4PP, or (ii) the formation of BrdUrd-labeled repair patches. No differences in repair capacity were observed between XP-D and XP-D-CS cells. In both cell types repair of CPD was completely absent whereas 6-4PP were inefficiently removed from the ADA gene and the 754 gene with similar kinetics. However, whereas XP-D cells were able to restore UV-inhibited RNA synthesis after a UV-dose of 2 J/m2, RNA synthesis in XP-D-CS cells remained repressed up to 24 h after irradiation. Our results are inconsistent with the hypothesis that differences in the capacity to perform preferential repair of UV-induced photolesions in active genes between XP-D and XP-D-CS cells are the cause of the extreme UV-sensitivity of XP-D-CS cells. Rather, the enhanced sensitivity of XP-D-CS cells may be associated with a defect in transcription regulation superimposed on the repair defect. (+info)
Mouse model for the DNA repair/basal transcription disorder trichothiodystrophy reveals cancer predisposition. (5/194)Patients with the nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) are highly predisposed to develop sunlight-induced skin cancer, in remarkable contrast to photosensitive NER-deficient trichothiodystrophy (TTD) patients carrying mutations in the same XPD gene. XPD encodes a helicase subunit of the dually functional DNA repair/basal transcription complex TFIIH. The pleiotropic disease phenotype is hypothesized to be, in part, derived from a repair defect causing UV sensitivity and, in part, from a subtle, viable basal transcription deficiency accounting for the cutaneous, developmental, and the typical brittle hair features of TTD. To understand the relationship between deficient NER and tumor susceptibility, we used a mouse model for TTD that mimics an XPD point mutation of a TTD patient in the mouse germline. Like the fibroblasts from the patient, mouse cells exhibit a partial NER defect, evident from the reduced UV-induced DNA repair synthesis (residual repair capacity approximately 25%), limited recovery of RNA synthesis after UV exposure, and a relatively mild hypersensitivity to cell killing by UV or 7,12-dimethylbenz[a]anthracene. In accordance with the cellular studies, TTD mice exhibit a modestly increased sensitivity to UV-induced inflammation and hyperplasia of the skin. In striking contrast to the human syndrome, TTD mice manifest a dear susceptibility to UV- and 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis, albeit not as pronounced as the totally NER-deficient XPA mice. These findings open up the possibility that TTD is associated with a so far unnoticed cancer predisposition and support the notion that a NER deficiency enhances cancer susceptibility. These findings have important implications for the etiology of the human disorder and for the impact of NER on carcinogenesis. (+info)
Potential roles for p53 in nucleotide excision repair. (6/194)Ultraviolet (UV) light-induced DNA damage is repaired by the nucleotide excision repair pathway, which can be subdivided into transcription-coupled repair (TCR) and global genome repair (GGR). Treatment of cells with a priming dose of UV light appears to stimulate both GGR and TCR, suggesting that these processes are inducible. GGR appears to be disrupted in p53-deficient fibroblasts, whereas the effect of p53 disruption on TCR remains somewhat controversial. Normal recovery of mRNA synthesis following UV irradiation is thought to depend on TCR. We have found that the recovery of mRNA synthesis following exposure to UV light is severely attenuated in p53-deficient human fibroblasts. Therefore, p53 disruption may lead to a defect in TCR or a post-repair process required for the recovery of mRNA synthesis. Several different functions of p53 have been proposed which could contribute to these cellular processes. We suggest that p53 could participate in GGR and the recovery of mRNA synthesis following UV exposure through the regulation of steady-state levels of one or more p53-regulated gene products important for these processes. Furthermore, we suggest that the role of p53 in the recovery of mRNA synthesis is important for resistance to UV-induced apoptosis. (+info)
The interpretation of optical coherence tomography images of the retina. (7/194)PURPOSE: To determine the relationship between optical coherence tomography (OCT) images of the retina and retinal substructure in vitro and in vivo. METHODS: In vitro, OCT images of human and bovine retina were acquired after sequential excimer laser ablation of the inner retinal layers. Measurements of bands in the OCT images were compared with measurements of retinal layers on histology of the ablated specimens. In vivo, OCT images were acquired of retinal lesions in which there was a displacement of pigmented retinal pigment epithelial (RPE) cells: retinitis pigmentosa and laser photocoagulation (eight eyes each). RESULTS: The mean thickness of human inner OCT bands (131 microm; 95% confidence interval [CI], 122-140 microm) was 7.3 times that of the retinal nerve fiber layer (RNFL). This band persisted despite ablation greater than 140 microm. The inner aspect of the outer OCT band corresponded to the apical RPE, but the mean thickness of this band in human tissue (55 microm; 95% CI, 48-62 microm) was 2.6 times the thickness of the RPE-choriocapillaris complex. OCT measurement of total retinal thickness was accurate (coefficient of variance, 0.05) and precise (coefficient of correlation with light microscopy, 0.98). Hyperpigmented lesions gave rise to high signal, attenuating deeper signal; hypopigmented lesions had the opposite effect on deeper signal. CONCLUSIONS: The inner band is not RNFL specific, partly consisting of a surface-related signal. The location, not thickness, of the outer band corresponds to RPE melanin. Given the additional effect of polarization settings, precise OCT measurement of specific retinal layers is currently precluded. (+info)
Oxidative damage-induced PCNA complex formation is efficient in xeroderma pigmentosum group A but reduced in Cockayne syndrome group B cells. (8/194)Proliferating cell nuclear antigen (PCNA), a processivity factor for DNA polymerases delta and epsilon, is essential for both DNA replication and repair. PCNA is required in the resynthesis step of nucleotide excision repair (NER). After UV irradiation, PCNA translocates into an insoluble protein complex, most likely associated with the nuclear matrix. It has not previously been investigated in vivo whether PCNA complex formation also takes place after oxidative stress. In this study, we have examined the involvement of PCNA in the repair of oxidative DNA damage. PCNA complex formation was studied in normal human cells after treatment with hydrogen peroxide, which generates a variety of oxidative DNA lesions. PCNA was detected by two assays, immunofluorescence and western blot analyses. We observed that PCNA redistributes from a soluble to a DNA-bound form during the repair of oxidative DNA damage. PCNA complex formation was analyzed in two human natural mutant cell lines defective in DNA repair: xeroderma pigmentosum group A (XP-A) and Cockayne syndrome group B (CS-B). XP-A cells are defective in overall genome NER while CS-B cells are defective only in the preferential repair of active genes. Immunofluorescent detection of PCNA complex formation was similar in normal and XP-A cells, but was reduced in CS-B cells. Consistent with this observation, western blot analysis in CS-B cells showed a reduction in the ratio of PCNA relocated as compared to normal and XP-A cells. The efficient PCNA complex formation observed in XP-A cells following oxidative damage suggests that formation of PCNA-dependent repair foci may not require the XPA gene product. The reduced PCNA complex formation observed in CS-B cells suggests that these cells are defective in the processing of oxidative DNA damage. (+info)
The symptoms of Cockayne syndrome can vary in severity and may include:
* Severe developmental delays and intellectual disability
* Poor muscle tone and coordination
* Vision and hearing loss
* Short stature
* Small head size (microcephaly)
* Abnormalities of the face and skull
* Increased risk of infections and cancer
There is no cure for Cockayne syndrome, and treatment is focused on managing the symptoms and preventing complications. This may include:
* Physical therapy to improve muscle tone and coordination
* Speech and language therapy to improve communication skills
* Occupational therapy to develop daily living skills
* Medications to manage seizures, if present
* Regular monitoring by a multidisciplinary team of healthcare professionals
The prognosis for individuals with Cockayne syndrome is generally poor, and many do not survive beyond early childhood. However, with appropriate medical care and support, some individuals with this condition may live into their teenage years or even longer.
It's important to note that Cockayne syndrome is a rare disorder, and it can be challenging to diagnose and manage. A thorough evaluation by a team of healthcare professionals, including a geneticist, is necessary for accurate diagnosis and appropriate management.
The main symptoms of XP include:
1. Extremely sensitive skin that burns easily and develops freckles and age spots at an early age.
2. Premature aging of the skin, including wrinkling and thinning.
3. Increased risk of developing skin cancers, especially melanoma, which can be fatal if not treated early.
4. Poor wound healing and scarring.
5. Eye problems such as cataracts, glaucoma, and poor vision.
6. Neurological problems such as intellectual disability, seizures, and difficulty with coordination and balance.
XP is usually inherited in an autosomal recessive pattern, which means that a child must inherit two copies of the mutated gene, one from each parent, to develop the condition. The diagnosis of XP is based on clinical features, family history, and genetic testing. There is no cure for XP, but treatment options include:
1. Avoiding UV radiation by staying out of the sun, using protective clothing, and using sunscreens with high SPF.
2. Regular monitoring and early detection of skin cancers.
3. Chemoprevention with drugs that inhibit DNA replication.
4. Photoprotection with antioxidants and other compounds that protect against UV damage.
5. Managing neurological problems with medications and therapy.
The prognosis for XP is poor, with most patients dying from skin cancer or other complications before the age of 20. However, with early diagnosis and appropriate treatment, some patients may be able to survive into their 30s or 40s. There is currently no cure for XP, but research is ongoing to develop new treatments and improve the quality of life for affected individuals.
There are several types of photosensitivity disorders, including:
1. Photodermatitis: This is a common condition that causes skin redness, itching, and blisters after exposure to UV radiation. It can be triggered by medications, certain plants, or even some cosmetics.
2. Solar urticaria: This condition causes hives and other skin symptoms after exposure to sunlight. The triggers can include not only UV radiation but also heat, wind, or cold.
3. Photosensitive epilepsy: This is a rare condition that can cause seizures in individuals who have a history of epilepsy. Exposure to certain types of light, especially flickering lights or bright colors, can trigger seizures.
4. Chronic actinic dermatitis: This condition causes skin inflammation and sensitivity to UV radiation, leading to redness, itching, and burning. It is more common in older adults and those with fair skin.
The symptoms of photosensitivity disorders can vary depending on the type of condition and the individual. Common symptoms include:
* Skin redness and irritation
* Itching and burning sensations
* Blisters or hives
* Swelling and inflammation
* Eye irritation or vision problems
* Headaches or fatigue
* Seizures (in the case of photosensitive epilepsy)
Photosensitivity disorders can be caused by a variety of factors, including:
1. Genetic predisposition: Some individuals may be more susceptible to photosensitivity due to their genetic makeup.
2. Medications: Certain medications, such as antibiotics and antipsychotics, can cause photosensitivity as a side effect.
3. Plants or other environmental factors: Exposure to certain plants or other environmental triggers can cause photosensitivity in some individuals.
4. Medical conditions: Certain medical conditions, such as lupus or porphyria, can increase the risk of developing photosensitivity.
There is no cure for photosensitivity disorders, but there are several treatment options available to help manage symptoms and prevent complications. These may include:
1. Avoiding triggers: Individuals with photosensitive conditions should avoid exposure to triggers such as sunlight or certain chemicals.
2. Protective clothing and gear: Wearing protective clothing and gear, such as hats and long sleeves, can help prevent skin exposure to UV radiation.
3. Medications: Topical creams and ointments, oral medications, or injectable treatments may be prescribed to manage symptoms such as itching and inflammation.
4. Phototherapy: Exposure to specific wavelengths of light, such as UVB or PUVA, can help improve skin conditions in some individuals.
5. Lifestyle modifications: Avoiding triggers, protecting the skin, and managing underlying medical conditions can help reduce the risk of complications associated with photosensitivity disorders.
It is important to note that photosensitivity disorders can be unpredictable, and the severity of symptoms can vary from person to person and over time. If you suspect you or someone you know may have a photosensitivity disorder, it is essential to consult with a healthcare professional for proper diagnosis and treatment.
Examples of syndromes include:
1. Down syndrome: A genetic disorder caused by an extra copy of chromosome 21 that affects intellectual and physical development.
2. Turner syndrome: A genetic disorder caused by a missing or partially deleted X chromosome that affects physical growth and development in females.
3. Marfan syndrome: A genetic disorder affecting the body's connective tissue, causing tall stature, long limbs, and cardiovascular problems.
4. Alzheimer's disease: A neurodegenerative disorder characterized by memory loss, confusion, and changes in personality and behavior.
5. Parkinson's disease: A neurological disorder characterized by tremors, rigidity, and difficulty with movement.
6. Klinefelter syndrome: A genetic disorder caused by an extra X chromosome in males, leading to infertility and other physical characteristics.
7. Williams syndrome: A rare genetic disorder caused by a deletion of genetic material on chromosome 7, characterized by cardiovascular problems, developmental delays, and a distinctive facial appearance.
8. Fragile X syndrome: The most common form of inherited intellectual disability, caused by an expansion of a specific gene on the X chromosome.
9. Prader-Willi syndrome: A genetic disorder caused by a defect in the hypothalamus, leading to problems with appetite regulation and obesity.
10. Sjogren's syndrome: An autoimmune disorder that affects the glands that produce tears and saliva, causing dry eyes and mouth.
Syndromes can be diagnosed through a combination of physical examination, medical history, laboratory tests, and imaging studies. Treatment for a syndrome depends on the underlying cause and the specific symptoms and signs presented by the patient.
Enophthalmos can cause a range of symptoms including:
* Diplopia (double vision)
* Blurred vision
* Eye strain and fatigue
* Difficulty moving the eyes
* Decreased vision in the affected eye
Enophthalmos is often diagnosed through a comprehensive eye exam, which includes a visual acuity test, refraction test, and imaging studies such as MRI or CT scans to rule out other conditions.
Treatment options for enophthalmos depend on the underlying cause of the condition. In some cases, glasses or contact lenses may be prescribed to correct refractive errors that contribute to the condition. Surgery may be necessary in more severe cases, such as when the condition is caused by a tumor or other structural abnormality. In other cases, prism lenses or eye muscle surgery may be recommended to help realign the eyes and improve vision.
Overall, enophthalmos is a rare and potentially vision-threatening condition that requires prompt medical attention from an eye care professional for proper diagnosis and treatment.
1. Medical Definition: In medicine, dwarfism is defined as a condition where an individual's height is significantly below the average range for their age and gender. The term "dwarfism" is often used interchangeably with "growth hormone deficiency," but the two conditions are not the same. Growth hormone deficiency is a specific cause of dwarfism, but there can be other causes as well, such as genetic mutations or chromosomal abnormalities.
2. Genetic Definition: From a genetic perspective, dwarfism can be defined as a condition caused by a genetic mutation or variation that results in short stature. There are many different genetic causes of dwarfism, including those caused by mutations in the growth hormone receptor gene, the insulin-like growth factor 1 (IGF1) gene, and other genes involved in growth and development.
3. Anthropological Definition: In anthropology, dwarfism is defined as a physical characteristic that is considered to be outside the normal range for a particular population or culture. This can include individuals who are short-statured due to various causes, including genetics, nutrition, or environmental factors.
4. Social Definition: From a social perspective, dwarfism can be defined as a condition that is perceived to be different or abnormal by society. Individuals with dwarfism may face social stigma, discrimination, and other forms of prejudice due to their physical appearance.
5. Legal Definition: In some jurisdictions, dwarfism may be defined as a disability or a medical condition that is protected by anti-discrimination laws. This can provide legal protections for individuals with dwarfism and ensure that they have access to the same rights and opportunities as others.
In summary, the definition of dwarfism can vary depending on the context in which it is used, and it may be defined differently by different disciplines and communities. It is important to recognize and respect the diversity of individuals with dwarfism and to provide support and accommodations as needed to ensure their well-being and inclusion in society.
There are several types of premature aging, including:
1. Progeria: This is a rare genetic condition that causes accelerated aging in children, resulting in a shortened life span.
2. Hutchinson-Gilford progeria syndrome: This is the most common form of progeria, which affects approximately 1 in 4 million children worldwide. Children with this condition typically die before reaching their teenage years due to complications such as heart attack or stroke.
3. Wiedemann-Steiner syndrome: This is a rare genetic disorder that causes premature aging, including wrinkled skin, thinning hair, and joint stiffness.
4. Werner syndrome: This is a rare genetic disorder that affects approximately 1 in 250,000 individuals worldwide. It is characterized by premature aging, including grey hair, wrinkled skin, and a high risk of developing cancer and other age-related diseases.
5. Telomere shortening: Telomeres are the protective caps at the end of chromosomes that shorten with each cell division. Premature telomere shortening can lead to accelerated aging and an increased risk of age-related diseases.
6. Chronic stress: Prolonged exposure to chronic stress can lead to premature aging, including changes in the brain, skin, and immune system.
7. Poor nutrition: A diet lacking essential nutrients can lead to premature aging, including vitamin D deficiency, which is associated with an increased risk of osteoporosis and other age-related diseases.
8. Lack of exercise: Physical inactivity can contribute to premature aging, including decreased muscle mass, bone density, and cognitive function.
9. Smoking: Cigarette smoking is a significant risk factor for premature aging, including wrinkles, age spots, and an increased risk of cancer and cardiovascular disease.
10. Alcohol consumption: Excessive alcohol consumption can lead to premature aging, including liver damage, heart disease, and certain types of cancer.
While many of these factors are beyond our control, there are steps we can take to reduce their impact and promote healthy aging. These include maintaining a balanced diet, exercising regularly, getting enough sleep, managing stress, not smoking, and limiting alcohol consumption. Additionally, staying up-to-date on preventative healthcare measures, such as regular check-ups and screenings, can help identify and address any potential health issues before they become more serious.
1. Epidermolysis bullosa (EB): A group of rare genetic disorders that affect the skin and mucous membranes, causing blisters and sores to form easily.
2. Ichthyosis: A group of genetic disorders that cause dry, thickened skin and scales to form.
3. Netherton syndrome: A rare genetic disorder that causes a combination of skin symptoms, including thinning of the skin, increased risk of infections, and difficulty healing wounds.
4. Pyoderma gangrenosum: A rare genetic disorder that causes painful, ulcerating sores on the skin.
5. X-linked dystonia-Episodes Myoclonus (XLDE): A rare genetic disorder that causes muscle spasms and movement problems, as well as skin symptoms such as thickened skin and difficulty swallowing.
6. Neurofibromatosis type 1: A genetic disorder that causes tumors to grow on nerve tissue, which can also affect the skin and cause symptoms such as freckling and skin thickening.
7. Tuberous sclerosis complex (TSC): A rare genetic disorder that causes non-cancerous growths (tumors) to form in organs such as the brain, heart, kidneys, and skin.
8. Vitiligo: An autoimmune disorder that causes the loss of pigment-producing cells (melanocytes) in the skin, leading to white patches.
9. Alopecia areata: An autoimmune disorder that causes hair loss, often starting with small patches on the scalp or face.
These are just a few examples of genetic skin diseases, and there are many more that can affect the skin in different ways. Treatment for these conditions varies depending on the specific diagnosis and severity of symptoms, but may include medications, lifestyle changes, or surgery to remove growths or improve appearance.
The term "trichothiodystrophy" was coined in the 1980s to describe a group of patients with similar clinical features, including trichodystrophic hair, cognitive impairment, and various other physical anomalies. Since then, several forms of TTD have been identified, each with distinct clinical features and genetic causes.
The most common forms of TTD include:
1. Trichothiodystrophy type 1 (also known as "classic" TTD): This is the most common form of TTD, accounting for about 70% of all cases. It is caused by mutations in the helicase-like protein 48 (HLF) gene, which plays a critical role in DNA repair and replication.
2. Trichothiodystrophy type 2 (TTD2): This form of TTD is caused by mutations in the gene encoding the enzyme p53-regulated protein (PRPS1). PRPS1 is involved in the regulation of protein synthesis and folding, and mutations in this gene can lead to a variety of developmental defects.
3. Trichothiodystrophy type 3 (TTD3): This form of TTD is caused by mutations in the gene encoding the enzyme mitochondrial DNA polymerase gamma (POLG). POLG is involved in the replication and repair of mitochondrial DNA, which is essential for the proper functioning of mitochondria.
Other forms of TTD include X-linked trichothiodystrophy (XLID), which affects males almost exclusively and is caused by mutations in the gene encoding the enzyme ornithine transcarbamylase (OTC); and trichothiodystrophy type 4 (TTD4), which is caused by mutations in the gene encoding the enzyme thymine dimer-specific photolyase (TDP1).
Trichothiodystrophy can have a wide range of symptoms, depending on the specific form of the disorder. These may include:
* Developmental delays and intellectual disability
* Skeletal abnormalities, such as short stature, scoliosis, and joint deformities
* Skin changes, such as photosensitivity, thinning of the skin, and pigmentary changes
* Vision problems, including cataracts, glaucoma, and progressive retinal degeneration
* Hearing loss
* Neurological problems, such as seizures, tremors, and ataxia (loss of coordination)
* Mitochondrial myopathy, which is a muscle disorder that can cause weakness, muscle wasting, and muscle cramps.
There is no cure for trichothiodystrophy, but treatment options are available to manage the symptoms. These may include:
* Medications to control seizures and other neurological problems
* Physical therapy to improve muscle strength and coordination
* Occupational therapy to improve daily functioning
* Speech therapy to improve communication skills
* Vision aids, such as glasses or contact lenses, to correct vision problems
* Surgery to correct skeletal abnormalities or other physical complications.
The prognosis for trichothiodystrophy varies depending on the specific form of the disorder and the severity of the symptoms. Some forms of the disorder may have a more favorable prognosis, while others may be associated with significant health problems and a shorter life expectancy. It is important for individuals with trichothiodystrophy to receive prompt and ongoing medical care to manage their symptoms and maximize their quality of life.
Down syndrome can be diagnosed before birth through prenatal testing, such as chorionic villus sampling or amniocentesis, or after birth through a blood test. The symptoms of Down syndrome can vary from person to person, but common physical features include:
* A flat face with a short neck and small ears
* A short stature
* A wide, short hands with short fingers
* A small head
* Almond-shaped eyes that are slanted upward
* A single crease in the palm of the hand
People with Down syndrome may also have cognitive delays and intellectual disability, as well as increased risk of certain medical conditions such as heart defects, gastrointestinal problems, and hearing and vision loss.
There is no cure for Down syndrome, but early intervention and proper medical care can greatly improve the quality of life for individuals with the condition. Treatment may include speech and language therapy, occupational therapy, physical therapy, and special education programs. With appropriate support and resources, people with Down syndrome can lead fulfilling and productive lives.
1. Abdominal obesity (excess fat around the waistline)
2. High blood pressure (hypertension)
3. Elevated fasting glucose (high blood sugar)
4. High serum triglycerides (elevated levels of triglycerides in the blood)
5. Low HDL cholesterol (low levels of "good" cholesterol)
Having three or more of these conditions is considered a diagnosis of metabolic syndrome X. It is estimated that approximately 34% of adults in the United States have this syndrome, and it is more common in women than men. Risk factors for developing metabolic syndrome include obesity, lack of physical activity, poor diet, and a family history of type 2 diabetes or CVD.
The term "metabolic syndrome" was first introduced in the medical literature in the late 1980s, and since then, it has been the subject of extensive research. The exact causes of metabolic syndrome are not yet fully understood, but it is believed to be related to insulin resistance, inflammation, and changes in body fat distribution.
Treatment for metabolic syndrome typically involves lifestyle modifications such as weight loss, regular physical activity, and a healthy diet. Medications such as blood pressure-lowering drugs, cholesterol-lowering drugs, and anti-diabetic medications may also be prescribed if necessary. It is important to note that not everyone with metabolic syndrome will develop type 2 diabetes or CVD, but the risk is increased. Therefore, early detection and treatment are crucial in preventing these complications.
Frederick Parkes Weber
Excision repair cross-complementing
Edward Alfred Cockayne
Nucleotide excision repair
DNA damage theory of aging
DNA repair-deficiency disorder
DNA-(apurinic or apyrimidinic site) lyase
Transcription factor II H
Evolution of ageing
List of diseases (C)
2020 New Year Honours
List of skin conditions
List of OMIM disorder codes
List of MeSH codes (C05)
List of syndromes
List of diseases (E)
List of neurological conditions and disorders
Cockayne syndrome - About the Disease - Genetic and Rare Diseases Information Center
Cockayne syndrome: MedlinePlus Genetics
Genetics of Cockayne Syndrome Medication
Cockayne syndrome: MedlinePlus Genetics
Cockayne Syndrome - PubMed
Cockayne Syndrome - MeSH - NCBI
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Defective DNA Repair1
- Many premature aging syndromes are due to defective DNA repair systems. (prolekarniky.cz)
- Four rare genetic diseases, xeroderma pigmentosum (XP), Cockayne syndrome (CS), the XP/CS complex and trichothiodystrophy (TTD) have defective DNA excision repair although only XP has increased cancer susceptibility. (nih.gov)
- Phenotypic variability in xeroderma pigmentosum group G: An uncommon case with severe prenatal-onset Cockayne syndrome features. (nih.gov)
- The endonuclease XPG is involved in repair of helix-distorting DNA lesions, and XPG defects cause the cancer-prone condition xeroderma pigmentosum (XP) alone or combined with the severe neurodevelopmental progeroid disorder Cockayne syndrome (CS). (prolekarniky.cz)
- Cockayne syndrome is caused by genetic changes in either the ERCC8 (CSA) or ERCC6 (CSB) genes. (nih.gov)
- Cockayne syndrome can result from mutations in either the ERCC6 gene (also known as CSB ) or the ERCC8 gene (also known as CSA ). (medlineplus.gov)
- High carriers frequency of an apparently ancient founder mutation p.Tyr322X in the ERCC8 gene responsible for Cockayne syndrome among Christian Arabs in Northern Israel. (bvsalud.org)
- ERCC8 is a WD repeat protein, which interacts with Cockayne syndrome type B (CSB) protein and with p44 protein, a subunit of the RNA polymerase II transcription factor IIH. (prosci-inc.com)
- To understand the relationship between TCR and expansion, we have crossed Fragile X premutation knock-in mice to mice with mutations in Cockayne syndrome group B (CSB), an important gene in the TCR pathway. (nih.gov)
- Mutations in this gene have been identified in patients with hereditary disease Cockayne syndrome (CS). (prosci-inc.com)
- Cockayne syndrome (CS) is a rare inherited human genetic disorder characterized by UV sensitivity, developmental abnormalities and premature aging. (hacettepe.edu.tr)
- Cockayne syndrome is a rare disease which causes short stature, premature aging (progeria), severe photosensitivity, and moderate to severe learning delay. (nih.gov)
- Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome. (nih.gov)
- My last major post traced developments related to a form of progeria (premature aging) known as Hutchinson-Gilford progeria syndrome , or HGPS , for short. (anti-agingfirewalls.com)
- There is also a different rare form of progeria known as Werner Syndrome (WS) that is worth looking at for what it might tell us about normal aging. (anti-agingfirewalls.com)
- Weidenheim KM, Dickson DW, Rapin I. Neuropathology of Cockayne syndrome: Evidence for impaired development, premature aging, and neurodegeneration. (medlineplus.gov)
- When Do Symptoms of Cockayne syndrome Begin? (nih.gov)
- Cockayne syndrome is sometimes divided into types I, II, and III based on the severity and age of onset of symptoms. (medlineplus.gov)
- If medical professionals did not diagnose or treat your cauda equina syndrome symptoms in time, you can claim for compensation. (thompsons.law)
- In fact, some of the genes known to be mutated in these syndromes can be mutated in patients with isolated RP. (mhmedical.com)
- Cockayne syndrome is a rare disorder characterized by an abnormally small head size (microcephaly), a failure to gain weight and grow at the expected rate (failure to thrive) leading to very short stature, and delayed development. (medlineplus.gov)
- Cockayne syndrome (CS) is a rare autosomal recessive disorder common in Christian Arabs due to a p.Tyr322X mutation . (bvsalud.org)
- BACKGROUND: Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by growth failure and multisystemic degeneration. (nih.gov)
- People with Cockayne syndrome have a serious reaction to an antibiotic medication called metronidazole. (medlineplus.gov)
- Some researchers highlight the roles of cell senescence and telomeres in WS: "Telomerase prevents the accelerated cell ageing of Werner syndrome fibroblasts( ref ). (anti-agingfirewalls.com)
- Cockayne syndrome type II is also known as cerebro-oculo-facio-skeletal (COFS) syndrome, and while some researchers consider it to be a separate but similar condition, others classify it as part of the Cockayne syndrome disease spectrum. (medlineplus.gov)
- Laugel V. Cockayne syndrome: the expanding clinical and mutational spectrum. (medlineplus.gov)
- The Cockayne Syndrome Natural History (CoSyNH) study: clinical findings in 102 individuals and recommendations for care. (medlineplus.gov)
- Intervention to correct mitochon reporting system to alert the leadership to organizational shortcomings that compro drial function in Cockayne Syndrome of the NIH Clinical Center about a variety mise patient safety. (nih.gov)
- This work was focused on molecular genetics, disease gene cloning, and genetic diagnosis of several rare disorders of the central nervous system (CNS), including Canavan disease, Hurler syndrome, and Hunter syndrome. (umassmed.edu)
- However, the localization of RAD51 to damage sites during TC-HR does not require BRCA1 and BRCA2, but relies on RAD52 and Cockayne Syndrome Protein B (CSB). (nature.com)
- The faulty DNA repair underlies photosensitivity in affected individuals, and researchers suspect that it also contributes to the other features of Cockayne syndrome. (medlineplus.gov)
- An amyloid fibrillar form of these peptides is the major component of amyloid plaques found in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (DOWN SYNDROME). (lookformedical.com)
- His diagnosis and treatment of cauda equina syndrome was delayed , resulting in life-long injuries including impaired mobility, numbness in his saddle area, genitals, and down the back of his legs, pain in his left leg, sexual dysfunction, and bladder and bowel dysfunction. (thompsons.law)
- Her concerns about numbness in her feet were ignored and a diagnosis of cauda equina syndrome was delayed. (thompsons.law)
- One member of this group of diseases is Fragile X syndrome (FXS), the most common cause of inherited intellectual disability. (nih.gov)
- This syndrome also includes failure to thrive, very small head (microcephaly), and impaired nervous system development. (nih.gov)
- However, in people with Cockayne syndrome, DNA damage is not repaired normally. (medlineplus.gov)
- Our solicitors have extensive experience of supporting people suffering from cauda equina syndrome resulting from medical negligence. (thompsons.law)
- Cockayne syndrome: review of 140 cases. (medlineplus.gov)
- It is essential that cauda equina syndrome is diagnosed and treated as soon as possible. (thompsons.law)