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Andrew G. Roberts - One of the best experts on this subject based on the ideXlab platform.
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co inheritance of mutations in the uroporphyrinogen decarboxylase and hemochromatosis genes accelerates the onset of Porphyria Cutanea Tarda
Journal of Investigative Dermatology, 2000Co-Authors: Jennifer J Brady, G.h. Elder, Andrew G. Roberts, Rhian R Morgan, Sharon D Whatley, Gareth Rowlands, Rosemarie Watson, Helen A Jackson, Mark Worwood, Cindy M DarbyAbstract:Porphyria Cutanea Tarda is a skin disease caused by photosensitization by porphyrins whose accumulation is caused by deficiency of hepatic uroporphyrin- ogen decarboxylase activity. Mutations in the uroporphyrinogen decarboxylase gene are present in the low-penetrant, autosomal dominant familial form but not in the commoner sporadic form of Porphyria Cutanea Tarda. We have investigated the relationship between age of onset of skin lesions and mutations (C282Y, H63D) in the hemochromatosis gene in familial (19 patients) and sporadic Porphyria Cutanea Tarda (65 patients). Familial Porphyria Cutanea Tarda was identified by mutational analysis of the uroporphyrinogen decarboxylase gene. Five previously described and eight novel mutations (A80S, R144P, L216Q, E218K, L282R, G303S, 402–403delGT, IVS2 + 2 delTAA) were identified. Homozygosity for the C282Y hemochromatosis mutation was associated with an earlier onset of skin lesions in both familial and sporadic Porphyria Cutanea Tarda, the effect being more marked in familial Porphyria Cutanea Tarda where anticipation was demonstrated in family studies. Analysis of the frequencies of hemochromatosis genotypes in each type of Porphyria Cutanea Tarda indicated that C282Y homozygosity is an important susceptibility factor in both types but suggested that heterozygosity for this mutation has much less effect on the development of the disease.
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increased frequency of the haemochromatosis cys282tyr mutation in sporadic Porphyria Cutanea Tarda
The Lancet, 1997Co-Authors: Andrew G. Roberts, Rhian R Morgan, Sharon D Whatley, Mark Worwood, George H ElderAbstract:Summary Background Sporadic Porphyria Cutanea Tarda is a skin disease associated with hepatic siderosis. Depletion of iron stores by phlebotomy is curative. The role of haemochromatosis genes in determining susceptibility to this disorder is controversial. We have examined the frequency in sporadic Porphyria Cutanea Tarda of mutations (Cys282Tyr, His63Asp) in a novel MHC class-I-like gene, one of which (Cys282Tyr) is believed to cause haemochromatosis. Methods 41 patients with sporadic Porphyria Cutanea Tarda, in whom the frequency of microsatellite alleles that define the ancestral haemochromatosis haplotype had previously been determined, and 101 healthy blood donors were studied for the presence of the Cys282Tyr and His63Asp mutations. We used restriction-enzyme digestion of PCR-amplified genomic DNA. Findings The Cys282Tyr mutation occurred in 18 (44%) of patients compared with 11 (11%) of controls (relative risk 6·2, 95% CI 2·6–14·5, p=0·00003). Seven (17%) patients, aged 48–79 years, were homozygotes. In 12 patients, the Cys282Tyr mutation was associated with markers of the HLA-A3-containing ancestral haemochromatosis haplotype. Ages at presentation were the same for those with or without the Cys282Tyr mutation. There was no difference in the frequency of the His63Asp mutation. Interpretation Inheritance of one or more haemochromatosis genes is an important susceptibility factor for sporadic Porphyria Cutanea Tarda. Some homozygotes for the Cys282Tyr mutation present late in life with Porphyria Cutanea Tarda, indicating that not all homozygotes present clinically with haemochromatosis. The relation between this genotype and disease needs further investigation.
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the frequency of hemochromatosis associated alleles is increased in british patients with sporadic Porphyria Cutanea Tarda
Hepatology, 1997Co-Authors: Andrew G. Roberts, Sharon D Whatley, Mark Worwood, Stuart A Nicklin, Jennifer J Pointon, Caroline Stone, G.h. ElderAbstract:The cause of the hepatic siderosis and iron overload that is common in Porphyria Cutanea Tarda (PCT) is uncertain. Heterozygosity for genetic hemochromatosis has been supported by some studies of the association between the HLA-A3 antigen and Porphyria Cutanea Tarda but not by others. The hemochromatosis gene is now believed to be located telomeric to HLA-A3 and close to the DNA microsatellite marker D6S1260. We have used this and other microsatellite markers, which together define an ancestral haplotype that is strongly linked to hemochromatosis, to reinvestigate the relationship between these disorders in 41 British patients with sporadic PCT. Fifteen patients carried the hemochromatosis-associated alleles D6S265-1 and D6S105-8. Four of these were homozygous for the ancestral haplotype D6S265-1: D6S105-8: D6S1260-4. We estimate that approximately 37% of British patients with sporadic PCT carry at least one hemochromatosis gene compared with 10% of the general population.
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a mutation g281e of the human uroporphyrinogen decarboxylase gene causes both hepatoerythropoietic Porphyria and overt familial Porphyria Cutanea Tarda biochemical and genetic studies on spanish patients
Journal of Investigative Dermatology, 1995Co-Authors: Andrew G. Roberts, C Herrero, Rafael Enriques De Salamanca, Mario Lecha, J M MascaroAbstract:Hepatoerythropoietic Porphyria is a severe cutaneous Porphyria caused by deficiency of uroporphyrinogen decarboxylase and is considered to be the homozygous form of familial (type II) Porphyria Cutanea Tarda. To elucidate further the relation between these conditions, we studied five Spanish families with hepatoerythropoietic Porphyria and nine unrelated Spanish patients with familial Porphyria Cutanea Tarda. Immunoreactive and catalytic uroporphyrinogen decarboxylase was decreased by greater than 95% in the five patients with hepatoerythropoietic Porphyria. Hepatic uroporphyrinogen decarboxylase activity was decreased to 22% of normal. Four patients were homozygous for a mutation (G281E) originally identified in a Tunisian family; the fifth patient was a compound heterozygote for this mutation. The calculated carrier frequency for G281E in Spain is one in 1800. None of the nine familial Porphyria Cutanea Tarda patients carried the G281E mutation. However, one G281E heterozygote in a family with hepatoerythropoietic Porphyria had overt Porphyria Cutanea Tarda. These findings suggest that the G281E mutation is functionally less severe than erythrocyte measurements indicate, that its clinical penetrance is very low in heterozygotes, and that, for this particular mutation, hepatoerythropoietic Porphyria is the homozygous form of familial Porphyria Cutanea Tarda.
C Herrero - One of the best experts on this subject based on the ideXlab platform.
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familial and sporadic Porphyria Cutanea Tarda clinical and biochemical features and risk factors in 152 patients
Medicine, 2010Co-Authors: Carlos Munozsantos, Antonio Guilabert, Nemesio Moreno, Jordi Tofigueras, Celia Badenas, Esteve Darwich, C HerreroAbstract:AbstractPorphyria Cutanea Tarda is the most frequent Porphyria and occurs in both sporadic and familial forms. We conducted the current study in a series of 152 consecutive patients with Porphyria Cutanea Tarda attending the Porphyria Unit of the Hospital Clinic of Barcelona, Spain, to update the cl
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familial and sporadic Porphyria Cutanea Tarda clinical and biochemical features and risk factors in 152 patients
Medicine, 2010Co-Authors: Carlos Munozsantos, Antonio Guilabert, Nemesio Moreno, Jordi Tofigueras, Celia Badenas, Esteve Darwich, C HerreroAbstract:Porphyria Cutanea Tarda is the most frequent Porphyria and occurs in both sporadic and familial forms. We conducted the current study in a series of 152 consecutive patients with Porphyria Cutanea Tarda attending the Porphyria Unit of the Hospital Clinic of Barcelona, Spain, to update the clinical manifestations of the disease and to study the sex differences, the proportion of familial forms, and the role of different risk factors in this population. Patients were classified as familial and sporadic cases according to erythrocyte uroporphyrinogen-decarboxylase activity and uroporphyrinogen-decarboxylase genotyping. In our cohort, skin fragility and blisters on the hands were the most frequent clinical manifestations. Women more frequently had facial hypertrichosis (84.8%; p = 0.004), affected areas other than the hands and face (33.3%; p = 0.008), and pruritus (27.3%; p = 0.041) compared with men. Of our patients, 11.8% did not present the typical clinical onset of the disease, with facial hypertrichosis and hyperpigmentation the more frequent complaints in these cases. Analysis of risk factors showed a high prevalence of hepatitis C virus infection (65.8%) and alcohol abuse (59.9%), both being more frequent in men (p < 0.001). Hepatitis C virus infection was the only risk factor that showed differences between the sporadic and familial forms in the logistic regression model (odds ratio, 0.05; 95% confidence interval, 0.006-0.46). In conclusion, atypical forms of presentation of Porphyria Cutanea Tarda should be considered in order to prevent delayed diagnosis. We note the sustained role of hepatitis C virus infection in the precipitation of sporadic Porphyria Cutanea Tarda. Therefore, in countries with a high prevalence of hepatitis C virus infection, the absence of such infection in a patient with Porphyria Cutanea Tarda may suggest a possible familial case.
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a mutation g281e of the human uroporphyrinogen decarboxylase gene causes both hepatoerythropoietic Porphyria and overt familial Porphyria Cutanea Tarda biochemical and genetic studies on spanish patients
Journal of Investigative Dermatology, 1995Co-Authors: Andrew G. Roberts, C Herrero, Rafael Enriques De Salamanca, Mario Lecha, J M MascaroAbstract:Hepatoerythropoietic Porphyria is a severe cutaneous Porphyria caused by deficiency of uroporphyrinogen decarboxylase and is considered to be the homozygous form of familial (type II) Porphyria Cutanea Tarda. To elucidate further the relation between these conditions, we studied five Spanish families with hepatoerythropoietic Porphyria and nine unrelated Spanish patients with familial Porphyria Cutanea Tarda. Immunoreactive and catalytic uroporphyrinogen decarboxylase was decreased by greater than 95% in the five patients with hepatoerythropoietic Porphyria. Hepatic uroporphyrinogen decarboxylase activity was decreased to 22% of normal. Four patients were homozygous for a mutation (G281E) originally identified in a Tunisian family; the fifth patient was a compound heterozygote for this mutation. The calculated carrier frequency for G281E in Spain is one in 1800. None of the nine familial Porphyria Cutanea Tarda patients carried the G281E mutation. However, one G281E heterozygote in a family with hepatoerythropoietic Porphyria had overt Porphyria Cutanea Tarda. These findings suggest that the G281E mutation is functionally less severe than erythrocyte measurements indicate, that its clinical penetrance is very low in heterozygotes, and that, for this particular mutation, hepatoerythropoietic Porphyria is the homozygous form of familial Porphyria Cutanea Tarda.
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is hepatitis c virus infection a trigger of Porphyria Cutanea Tarda
The Lancet, 1993Co-Authors: C Herrero, Asuncion Vicente, Jose M Mascaro, M Bruguera, J M Barrera, J Teres, J Rodes, M G Ercilla, Josep VidalAbstract:Porphyria Cutanea Tarda (PCT) is nearly always associated with hepatic dysfunction, but the reasons for the development and progression of the PCT-related liver disease are yet to be clarified. We investigated 100 patients with PCT for serologic markers of hepatitis C virus (HCV). Anti-HCV was present in 79% of 95 patients with acquired PCT, but in none of 5 patients with familial PCT. RIBA test was positive in all ELISA-reactive samples, and all 18 cases examined were HCV-RNA-positive. A correlation was found between the severity of liver disease and the prevalence of anti-HCV (20% in non-inflammatory changes, 60% in portal hepatitis, 97% in periportal hepatitis, and 100% in cirrhosis and hepatocellular carcinoma). In conclusion, HCV infection seems to be responsible for the inflammatory changes of the liver in patients with PCT and for the progression of liver disease, possibly evolving to hepatocellular carcinoma.
Flemming Brandrup - One of the best experts on this subject based on the ideXlab platform.
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familial and sporadic Porphyria Cutanea Tarda clinical biochemical and genetic features with emphasis on iron status
Acta Dermato-venereologica, 2003Co-Authors: Anette Bygum, M Horder, Niels Erik Petersen, Lene Christiansen, Kristian Thomsen, Flemming BrandrupAbstract:The manifestation of Porphyria Cutanea Tarda reflects genetic and environmental factors. Mutations in the uroporphyrinogen decarboxylase gene, located at chromosome 1p34, discriminate familial Porphyria Cutanea Tarda from sporadic cases. Furthermore, mutations in the haemochromatosis gene may be involved in the aetiology. In this study 53 unrelated Danish patients with Porphyria Cutanea Tarda were classified according to uroporphyrinogen decarboxylase and haemochromatosis gene mutations and the genotype related to the clinical and biochemical data. Thirteen patients (25%) had familial Porphyria Cutanea Tarda. The results signify the advantage of DNA diagnostics for identification of familial cases, as anamnestic data are doubtful and erythrocyte uroporphyrinogen decarboxylase activity measurements insufficient for correct classification. Eight patients with Porphyria Cutanea Tarda (15%) were homozygous for the haemochromatosis gene C282Y mutation and 8 patients were heterozygous. Patients homozygous for the haemochromatosis related mutation showed biochemical evidence of excessive iron storage as well as increased urine porphyrin excretion levels. This seems to confirm a relationship between Porphyria Cutanea Tarda and haemochromatosis. No differences were found between patients with sporadic and familial Porphyria Cutanea Tarda regarding age of onset, clinical severity, sex distribution, liver function tests and iron storage parameters. However, daily alcohol intake and use of oestrogens were reported more frequently in the group of sporadic patients. It was found that women were over-represented in our study.
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association between cyp1a2 polymorphism and susceptibility to Porphyria Cutanea Tarda
Human Genetics, 2000Co-Authors: Lene Christiansen, Flemming Brandrup, Anette Bygum, A Jensen, K Thomsen, M Horder, Niels Erik PetersenAbstract:Individuals with the most common form of the Porphyrias, Porphyria Cutanea Tarda (PCT), are believed to be genetically predisposed to development of clinically overt disease through mutations and polymorphisms in genes associated with known precipitating factors. In this study, we have examined a group of Danish patients with PCT for the presence of the C/A polymorphism in intron 1 of CYP1A2. The results demonstrate that the frequency of the highly inducible A/A genotype is increased in both familial and sporadic PCT. This suggests that inheritance of this genotype is a susceptibility factor in development of PCT.
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uroporphyrinogen decarboxylase gene mutations in danish patients with Porphyria Cutanea Tarda
Scandinavian Journal of Clinical & Laboratory Investigation, 2000Co-Authors: L Christiansen, Flemming Brandrup, Anette Bygum, A Jensen, K Thomsen, M Horder, Niels Erik PetersenAbstract:Decreased uroporphyrinogen decarboxylase (UROD) activity is a characteristic feature of the most common of the Porphyrias, Porphyria Cutanea Tarda (PCT). A subgroup of the clinically overt PCT cases is associated with mutations in the gene encoding UROD and inherited as an autosomal-dominant trait. In this study, DNAs from 53 Danish PCT patients were subjected to genetic analysis for UROD mutations using denaturing gradient gel electrophoresis. Eleven genetic variations, seven of which are possible disease causing, were identified. All but one of these mutations were previously unknown, lending further support to the assumption that PCT is a heteroallelic disease. Only 11% of the examined patients were previously recognized as familial PCT cases. However, possible disease-related UROD mutations were identified in 24% of the examined patients, indicating that genetic analysis of PCT patients may improve differentiation between familial and sporadic PCT cases.
Niels Erik Petersen - One of the best experts on this subject based on the ideXlab platform.
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familial and sporadic Porphyria Cutanea Tarda clinical biochemical and genetic features with emphasis on iron status
Acta Dermato-venereologica, 2003Co-Authors: Anette Bygum, M Horder, Niels Erik Petersen, Lene Christiansen, Kristian Thomsen, Flemming BrandrupAbstract:The manifestation of Porphyria Cutanea Tarda reflects genetic and environmental factors. Mutations in the uroporphyrinogen decarboxylase gene, located at chromosome 1p34, discriminate familial Porphyria Cutanea Tarda from sporadic cases. Furthermore, mutations in the haemochromatosis gene may be involved in the aetiology. In this study 53 unrelated Danish patients with Porphyria Cutanea Tarda were classified according to uroporphyrinogen decarboxylase and haemochromatosis gene mutations and the genotype related to the clinical and biochemical data. Thirteen patients (25%) had familial Porphyria Cutanea Tarda. The results signify the advantage of DNA diagnostics for identification of familial cases, as anamnestic data are doubtful and erythrocyte uroporphyrinogen decarboxylase activity measurements insufficient for correct classification. Eight patients with Porphyria Cutanea Tarda (15%) were homozygous for the haemochromatosis gene C282Y mutation and 8 patients were heterozygous. Patients homozygous for the haemochromatosis related mutation showed biochemical evidence of excessive iron storage as well as increased urine porphyrin excretion levels. This seems to confirm a relationship between Porphyria Cutanea Tarda and haemochromatosis. No differences were found between patients with sporadic and familial Porphyria Cutanea Tarda regarding age of onset, clinical severity, sex distribution, liver function tests and iron storage parameters. However, daily alcohol intake and use of oestrogens were reported more frequently in the group of sporadic patients. It was found that women were over-represented in our study.
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association between cyp1a2 polymorphism and susceptibility to Porphyria Cutanea Tarda
Human Genetics, 2000Co-Authors: Lene Christiansen, Flemming Brandrup, Anette Bygum, A Jensen, K Thomsen, M Horder, Niels Erik PetersenAbstract:Individuals with the most common form of the Porphyrias, Porphyria Cutanea Tarda (PCT), are believed to be genetically predisposed to development of clinically overt disease through mutations and polymorphisms in genes associated with known precipitating factors. In this study, we have examined a group of Danish patients with PCT for the presence of the C/A polymorphism in intron 1 of CYP1A2. The results demonstrate that the frequency of the highly inducible A/A genotype is increased in both familial and sporadic PCT. This suggests that inheritance of this genotype is a susceptibility factor in development of PCT.
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uroporphyrinogen decarboxylase gene mutations in danish patients with Porphyria Cutanea Tarda
Scandinavian Journal of Clinical & Laboratory Investigation, 2000Co-Authors: L Christiansen, Flemming Brandrup, Anette Bygum, A Jensen, K Thomsen, M Horder, Niels Erik PetersenAbstract:Decreased uroporphyrinogen decarboxylase (UROD) activity is a characteristic feature of the most common of the Porphyrias, Porphyria Cutanea Tarda (PCT). A subgroup of the clinically overt PCT cases is associated with mutations in the gene encoding UROD and inherited as an autosomal-dominant trait. In this study, DNAs from 53 Danish PCT patients were subjected to genetic analysis for UROD mutations using denaturing gradient gel electrophoresis. Eleven genetic variations, seven of which are possible disease causing, were identified. All but one of these mutations were previously unknown, lending further support to the assumption that PCT is a heteroallelic disease. Only 11% of the examined patients were previously recognized as familial PCT cases. However, possible disease-related UROD mutations were identified in 24% of the examined patients, indicating that genetic analysis of PCT patients may improve differentiation between familial and sporadic PCT cases.
Sandberg Sverre - One of the best experts on this subject based on the ideXlab platform.
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Illness Perception and Psychological Distress in Persons with Porphyria Cutanea Tarda
'Acta Dermato-Venereologica', 2016Co-Authors: Andersen Janice, Nordin Karin, Sandberg SverreAbstract:Porphyria Cutanea Tarda (PCT) requires long-term treatment and follow-up, although many patients experience life-long remission. The aim of this cross-sectional postal survey was to describe and investigate the association between illness perception, health complaints, self-reported symptoms and distress in persons with PCT. The participants perceived PCT as a chronic condition with high levels of personal and treatment control. Persons who reported active symptoms scored higher on perceived illness threat, total health complaints and psychological distress compared with those in remission or latent phases. However, a higher perception of illness threat and the total burden of health complaints were more closely associated with psychological distress than were perceived PCT symptoms activity. This has implications for clinical consultation; dermatologists should be attentive to symptoms activity, but also recognize that patients in remission with a high perceived illness threat and multiple health complaints might be especially vulnerable to psychological distress with regards to PCT. Key words: Porphyria Cutanea Tarda; illness perception; psychological distress; subjective health complaints; psychosocial
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Illness Perception and Psychological Distress in Persons with Porphyria Cutanea Tarda
'Acta Dermato-Venereologica', 2016Co-Authors: Andersen Janice, Nordin Karin, Sandberg SverreAbstract:Porphyria Cutanea Tarda (PCT) requires long-term treatment and follow-up, although many patients experience life-long remission. The aim of this cross-sectional postal survey was to describe and investigate the association between illness perception, health complaints, self-reported symptoms and distress in persons with PCT. The participants perceived PCT as a chronic condition with high levels of personal and treatment control. Persons who reported active symptoms scored higher on perceived illness threat, total health complaints and psychological distress compared with those in remission or latent phases. However, a higher perception of illness threat and the total burden of health complaints were more closely associated with psychological distress than were perceived PCT symptoms activity. This has implications for clinical consultation; dermatologists should be attentive to symptoms activity, but also recognize that patients in remission with a high perceived illness threat and multiple health complaints might be especially vulnerable to psychological distress with regards to PCT. Key words: Porphyria Cutanea Tarda; illness perception; psychological distress; subjective health complaints; psychosocial.publishedVersio