Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wilson's disease is a rare autosomal recessive inherited disorder of copper metabolism. Hepatic excretion of copper is impaired due to mutation of the gene for a copper-transporting adenosine triphosphatase, ATP7B. Copper accumulation in liver, brain, and other tissues may cause a wide spectrum of hepatic, neuropsychiatric, and other clinical manifestations. The diagnosis may be supported by measurement of serum ceruloplasmin, urinary copper excretion, and hepatic copper content as well as by detection of Kayser-Fleischer rings. Several treatments are available to increase urinary excretion and decrease intestinal absorption of copper.
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PMID:Wilson's disease: copper unfettered. 1040 26

A major obstacle in the treatment of human solid carcinomas is the intrinsic/acquired resistance to cisplatin-based chemotherapy. Copper-transporting P-type adenosine triphosphatase (ATP7B) has been reported to be associated with cisplatin resistance in vitro. ATP7B is overexpressed in human solid carcinomas such as breast, gastric and oral squamous cell carcinomas. ATP7B expression has an influential effect on some subsets of patients with cisplatin-treated carcinomas. ATP7B mutation is well-known as a cause of Wilson's disease. In addition, the six copper-binding domain and ATP-binding domain of ATP7B are important for the transportation of metals. Therefore, we performed the mutation analysis at the six copper-binding domain and ATP-binding domain of ATP7B. No mutation at the six copper-binding domain and ATP-binding domain was observed in breast, gastric and oral squameous cell carcinomas. These results indicate that the analysis of the ATP7B gene and/or protein will be helpful for the choice of chemotherapy in patients with human solid carcinomas.
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PMID:Mutation analysis of copper-transporting P-type adenosine triphosphatase (ATP7B) in human solid carcinomas. 1282 Apr 78

Wilson's disease is a rare genetic condition, transmitted on a recessive autosomal mode, which involves a disturbance of copper metabolism. Its prevalence is 1: 30000. It is treatable but may be lethal if not managed early and treated adequately. It is caused by the loss of function of an adenosine triphosphatase (ATP 7B), which is due to a mutation in the ATP 7B gene on chromosome 13. This leads to a decrease or absence of copper transport to the bile and its accumulation within certain organs, particularly the liver and the brain. In this article we present two cases of Wilson's disease in two young male patients. We also briefly review the pathophysiology of the illness, discuss the latest guidelines for diagnosis and treatment and outline the recent genetic discoveries.
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PMID:[Wilson's disease: Clinical presentations]. 1621 3

Wilson's disease is an infrequent, autosomic recessive pathology, resulting from a loss of function of an adenosine triphosphatase (ATP7B or WDNP), secondarily to a change (more than 60 are described currently), insertion or deletion of the ATP7B gene located on the chromosome 13q14.3-q21.1, which involves a reduction or an absence of the transport of copper in the bile and its accumulation in the body, notably the brain. Wilson's disease is transmitted by an autosomic recessive gene located on the long arm of chromosome 13. The prevalence of the heterozygote is evaluated at 1/90 and the homozygote at 1/30,000. Consanguinity, frequent in the socially geographically isolated populations, increases the prevalence of the disease. The toxic quantities of copper, which accumulate in the liver since early childhood and perhaps before, remain concentrated in the body for years. Hence, cytological and histological modifications can be detected in the biopsies, before the appearance of clinical or biological symptoms of hepatic damage. The accumulation of copper in the liver is due to a defect in the biliary excretion of metal and is accompanied invariably by a deficit in ceruloplasmin; protein synthesized from a transferred ATP7B gene, which causes retention of the copper ions in the liver. The detectable cellular anomalies are of two types: hepatic lesions resulting in acute hepatic insufficiency, acute hepatitis and finally advanced cirrhosis and lesions of the central nervous system responsible for the neurological and psychiatric disorders. In approximately 40-50% of the patients, the first manifestation of Wilson's disease affects the central nervous system. Although copper diffuses in the liver towards the blood and then towards other tissues, it has disastrous consequences only in the brain. It can therefore cause either a progressive neurological disease, or psychiatric disorders. Wilson's disease begins in the form of a hepatic, neurological, or psychiatric disease in at least 90% of the patients. In some rare cases, the first manifestations of the disease can be psychiatric which, according to the literature, accounts for only 10% of the cases. The disease can be revealed by isolated behavioral problems, an irrational syndrome, a schizophrenic syndrome, or a manic-depressive syndrome. Damage to the central nervous system can be more severe, thus, several differential diagnoses have been discussed: a psychotic disorder of late appearance; a depressive state; a mental confusion disorder. The clinical syndrome is complex. Indeed, it is the polymorphism, which dominates in the description of the psychiatric demonstrations of the disease. This can lead to prejudicial diagnostic wandering, particularly since heavy sedative treatment may be required to suppress behavioral problems. Clinically, Wilson's disease generally appears between the age of 10 and 20. It rarely remains masked until after the age of 40. The first manifestations are hepatic (40% of the cases), neurological (35%) or psychiatric (10%). The inaugural disorder can finally take on a haematological, renal, or mixed form in approximately 15% of the cases. We have detailed the principal clinical elements. In approximately 40-50% of the patients, the first manifestation of the disease affects the central nervous system, where it can cause either a progressive neurological disease, or psychiatric disorders. The ophthalmologic disorder is dominated by Kayser-Fleischer's ring, representing a green or bronze colored ring on the periphery of the cornea. It occupies the higher pole of the cornea, then the lower pole, and extends to the whole circumference. It is generally only visible under examination with a slit lamp. It disappears on average within 3-5 years following copper chelating therapy. Kayser-Fleischer's ring has been described other than in Wilson's disease, in exceptional cases of prolonged cholestasis. On haematological level, the hyperhaemolysis is due to the toxicity of the ionic copper, released massively in the plasma by hepatocellular necrosis. The other manifestations can be found in the following organs: renal, osteoarticular, cardiac, endocrine, cutaneous, and in the teguments. Until 1952, the diagnosis was evoked only on clinical symptomatology. It can henceforth be marked unambiguous, even in the absence of any symptom, by the description of a ceruloplasmin plasma concentration of less than 200 ml/l, and of a Kayser-Fleischer's ring. Hepatic copper on sample is constantly increased during the disease (from 3 to 25 micromol/g of dry weight). On the other hand, the absence of a reduction in the plasma ceruloplasmin does not make it possible to exclude the diagnosis. Conversely, a reduction in ceruloplasmin can exist other than in Wilson's disease (nephritic syndrome, malabsorption syndrome, or severe hepatic insufficiency). Kayser-Fleischer's ring is quasiconstant among patients with neuropsychiatric demonstrations (thus, its absence represents a very strong argument against the diagnosis). It can on the other hand be lacking during hepatic forms, and in this case, its absence is not an argument against the diagnosis. Magnetic resonance imaging can reveal abnormal signals of the grey cores. A genetic study is conducted by liaison analysis in the event of a family history of the disease. When it is not treated, Wilson's disease induces lesions of the tissues, the outcome of which is always fatal. Treatment relies on the regulation of copper chelation, which improves the prognosis, and zinc, which captures the copper in a nontoxic form. The severe psychiatric disorders observed during Wilson's disease may require tranquilizers, but care should be taken because of potential neurological or hepatic side effects. Lithium seems an interesting treatment and remains theoretically indicated, taking into account the scarcity of the extrapyramidal symptoms and the hepatic dysfunction among patients at the stage of cirrhosis, since it is not metabolized in the liver. Although rare, it is important to approach Wilson's disease in psychiatry because the psychiatric manifestations can precede the somatic disorders and help to pose the diagnosis. We stress the importance of the early diagnosis of the pathology, the outcome of which is fatal in the absence of specific treatment.
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PMID:[The onset of psychiatric disorders and Wilson's disease]. 1878 84

Wilson's disease (WD) is an autosomal recessive disorder characterized by the functional disruption of the copper-transporting protein adenosine triphosphatase 7B (ATP-ase 7B). The disease is caused by mutations in ATP7B gene. It seems that the type of mutation in ATP7B only to some degree determines phenotypic manifestation of WD. We examined two pairs of monozygotic twins discordant for WD phenotype. The first set of twins were ATP7B compound heterozygotes c.3207C>A (p.H1069Q)/c.1211_1212insA (p.N404Kfs). The index case developed severe liver failure followed by depressive symptoms, dysarthria, and tremor at the age of 36. Her sister remained presymptomatic at diagnosis at the age of 39. The second twins were ATP7B c.3207C.A (p.H1069Q) homozygotes. The index case presented with dysarthria and tremor at the age of 26. Her sister remained clinically presymptomatic at diagnosis at the age of 28. We concluded that the phenotypic characteristics of WD are possibly attributable to epigenetic/environmental factors.
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PMID:Monozygotic female twins discordant for phenotype of Wilson's disease. 1930 78

Wilson's disease (WD) is an autosomal recessive disorder characterized by the functional disruption of adenosine triphosphatase 7B (ATP7B), which results in positive copper balance. Although the primary manifestations of the disease are hepatic or neurological in scope, the factors that cause a very diverse picture of WD are not well researched. We compared the first clinical presentation, ages of onset and diagnosis, copper metabolism parameters, and ceruloplasmin levels between index cases (ICs) and their siblings. We examined 73 ICs and 95 siblings from 73 families, including a total of 168 patients with biochemical and genetically confirmed WD diagnoses. We observed an 86% concordance rate of primary clinical symptoms among ICs with hepatic symptoms and their siblings. There was 66% concordance among ICs with neurological symptoms and their siblings. No differences regarding age at onset of symptoms or copper metabolism parameters at diagnosis were identified between hepatic ICs and their siblings. The age at symptom onset did not differ between neurological ICs and their siblings, although ICs presented lower ceruloplasmin and serum copper levels. These results demonstrate a high intra-familial concordance of the clinical and biochemical presentation of WD, suggesting that similar factors shared within the same families strongly influence the disease presentation.
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PMID:Concordance rates of Wilson's disease phenotype among siblings. 2377 50

Wilson's disease (WD), also known as hepatolenticular degeneration, is an autosomal recessive inherited disorder resulting from abnormal copper metabolism. Reduced copper excretion causes an excessive deposition of the copper in many organs such as the liver, central nervous system (CNS), cornea, kidney, joints, and cardiac muscle where the physiological functions of the affected organs are impaired. The underlying molecular mechanisms for WD have been extensively studied. It is now believed that a defect in P-type adenosine triphosphatase (ATP7B), the gene encoding the copper transporting P-type ATPase, is responsible for hepatic copper accumulation. Deposited copper in the liver produces toxic effects via modulating several molecular pathways. WD can be a lethal disease if left untreated. A better understanding of the molecular mechanisms causing the aberrant copper deposition and organ damage is the key to developing effective management approaches.
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PMID:Wilson's disease: a comprehensive review of the molecular mechanisms. 2580 4

Copper-transporting P-type adenosine triphosphatase (ATP7B) has been identified as the pathogenic gene in hepatolenticular degeneration, or Wilson's disease (WD). The aim of this study was to explore the correlation between genetic mutations and the clinical profile of WD, and to discuss the value of mutation examination in its diagnosis for providing a scientific basis for the development of a method to examine genetic mutations. Sixty-eight Chinese Han patients with WD and 20 controls were included in this study. The ATP7B gene in DNA extracted from patient blood samples was amplified by PCR and sequenced. These sequences were compared against corresponding gene sequences obtained from healthy controls to statistically analyze the genetic mutations. Five of the nineteen mutations in ATP7B were newly detected mutations; moreover, 8 of these mutations were polymorphic (2 were newly identified). The Arg778Leu and Pro992Leu mutations in exons 8 and 13 were detected at the highest mutation frequencies of 25.74 and 16.91%, respectively. The frequencies of all other mutations were below 5%. However, the clinical manifestations of WD did not differ significantly in patients with the Arg778Leu and Pro992Leu mutations. Therefore, these mutations were considered as hotspot mutations in Chinese WD patients. However, we observed no significant correlation between these genetic types and the clinical symptoms of WD. The correlation between the mutation genotype and disease phenotype remains to be elucidated. In conclusion, the highly sensitive and specific direct DNA sequencing method can be used to screen for the causative genes of WD.
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PMID:Direct sequencing of mutations in the copper-transporting P-type adenosine triphosphate (ATP7B) gene for diagnosis and pathogenesis of Wilson's disease. 2770 81