Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene

Méndez, Manuel; Poblete‐Gutiérrez, Pamela; García‐Bravo, María; Wiederholt, T.; Morán-Jiménez, María-Josefa; Garrido-Astray, M.C.; Frank, Jorge; Fontanellas, Antonio; Salamanca, Rafael Enrı́quez de

doi:10.1111/j.1365-2133.2007.08064.x

Cited by 19 publications

(10 citation statements)

References 36 publications

(58 reference statements)

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“…The largest of these studies (1 ) identified 19 fPCT cases in 84 patients, but because DNA analysis was performed only in patients with low UROD activity, the frequency of fPCT might have been underestimated by a few percent. The 2 other studies reported the familial form to constitute about 25% of cases when UROD gene analysis was performed in all patients [53 and 61 patients, respectively (3,5 )], whereas 9 of 18 PCT patients in a Chilean study had familial disease (6 ). Most (74%) of the fPCT cases in our study were caused by 2 frequently occurring mutations, c.578GϾC and c.636ϩ1GϾC.…”

Section: Discussionmentioning

confidence: 42%

“…Porphyria cutanea tarda (PCT) 5 is a disorder of porphyrin metabolism with associated skin photosensitivity that usually presents with vesiculobullous eruptions on the hands and face, and signs of liver damage. The disease is caused by a deficiency in uroporphyrinogen decarboxylase (UROD), the fifth enzyme in the heme synthesis pathway, and can be classified into several types, familial PCT (fPCT) and sporadic PCT (sPCT) being the most common.…”

confidence: 99%

“…The disease is caused by a deficiency in uroporphyrinogen decarboxylase (UROD), the fifth enzyme in the heme synthesis pathway, and can be classified into several types, familial PCT (fPCT) and sporadic PCT (sPCT) being the most common. fPCT, an autosomal dominant disorder of low penetrance characterized by low UROD activity in all cells, constitutes about 25% of the cases in most populations (1)(2)(3)(4)(5)(6)(7). The level of UROD activity in erythrocytes has traditionally been used to distinguish between fPCT and sPCT, because sPCT shows reduced UROD activity only in the liver.…”

confidence: 99%

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Familial and Sporadic Porphyria Cutanea Tarda: Characterization and Diagnostic Strategies

2009

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Background: Porphyria cutanea tarda (PCT) occurs in sporadic (sPCT) and familial (fPCT) forms, which are generally clinically indistinguishable and have traditionally been differentiated by erythrocyte uroporphyrinogen decarboxylase (UROD, EC 4.1.1.37) activity. We used UROD gene sequencing as the reference standard in assessing the diagnostic accuracy of UROD activity, evaluating the mutation spectrum of the UROD gene, determining the frequency and disease attributes of PCT and its subtypes in Norway, and developing diagnostic models that use clinical and laboratory characteristics for differentiating fPCT and sPCT. Methods: All consecutive patients with PCT diagnosed within a 6-year period were used for incidence calculations. UROD activity analysis, UROD gene sequencing, analysis of hemochromatosis mutations, and registration of clinical and laboratory data were carried out for 253 patients. Results: Fifty-three percent of the patients had disease-relevant mutations, 74% of which were c.578G>C or c.636+1G>C. The UROD activity at the optimal cutoff had a likelihood ratio (LR) of 9.2 for fPCT, whereas a positive family history had an LR of 19. A logistic regression model indicated that low UROD activity, a high uroporphyrin-heptaporphyrin ratio, a young age at diagnosis, male sex, and low alcohol consumption were predictors of fPCT. The incidence of PCT was 1 in 100 000. Conclusions: Two commonly occurring mutations are responsible for the high frequency of fPCT in Norway. UROD activity has a high diagnostic accuracy for differentiating the 2 PCT types, and a model that takes into account both clinical information and laboratory test results can be used to predict fPCT.

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Section: Discussionmentioning

confidence: 42%

confidence: 99%

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Familial and Sporadic Porphyria Cutanea Tarda: Characterization and Diagnostic Strategies

2009

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“…It is generally admitted that patient with erythrocytic activity lower than half of the value in controls have a partially inherited defect in UROD, and should be classified as having familial PCT [35]. It would therefore be interesting to study UROD gene mutations, as the results might be discordant between enzymatic and molecular analysis [1]. …”

Section: Discussionmentioning

confidence: 99%

“…There are 3 similar clinical types of PCT [1], the most common being the sporadic form (type I) and the familial autosomal-dominant form (type II), which is characterized by decreased hepatic and erythrocytic UROD activity. In the less frequent type III, there is also familial history of PCT, but UROD activity is decreased only in the liver.…”

Section: Introductionmentioning

confidence: 99%

Porphyria Cutanea Tarda, Hepatitis C, Uroporphyrinogen Decarboxylase and Mutations of HFE Gene

Cribier¹,

Chiavérini²,

Dali‐Youcef³

et al. 2008

Dermatology

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Background: Hemochromatosis gene (HFE) mutations and the hepatitis C virus (HCV) are known risk factors for porphyria cutanea tarda (PCT), but interactions with erythrocytic uroporphyrinogen decarboxylase (UROD) have seldom been addressed. Objective: In order toexamine the links between these factors, we conducted a multicentre prospective case-control study. Methods: PCT patients with (n = 32) or without HCV (n = 28) were matched to HCV+ (n = 32) and HCV– controls (n = 28). HFE mutations (C282Y and H63D) were analyzed by PCR. Results: PCT+/HCV+ patients were younger than PCT+/HCV– patients (46.9 vs. 58.2 years, p < 0.001). UROD values were not significantly different in HCV+ and HCV– patients. Both C282Y and H63D were more frequent in PCT+ patients than in controls, but there was no difference in HFE genotype according to HCV seropositivity. Mean UROD was lower in case of HFE mutations in both PCT patients and controls. Conclusion: In French patients, HCV infection is probably the major causal factor of PCT. It is not linked with HFE mutations, although they are significantly associated with PCT. A low erythrocytic UROD might be a predisposing factor. The UROD value was lower in patients with HFE mutations, suggesting a possible interaction between HFE genotype and UROD levels.

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Hepatoerythropoietic Porphyria and Familial Porphyria Cutanea Tarda in Spanish Patients: G281E Mutation in the Uroporphyrinogen Decarboxylase Gene

Darwich¹,

To‐Figueras²,

Badenas³

et al. 2010

Arch Dermatol

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Molecular heterogeneity of familial porphyria cutanea tarda in Spain: characterization of 10 novel mutations in the UROD gene

Abstract: These results confirm the high degree of molecular heterogeneity of F-PCT in Spain and emphasize the usefulness of molecular genetic analysis to distinguish between F-PCT and S-PCT.

Cited by 19 publications

References 36 publications

Familial and Sporadic Porphyria Cutanea Tarda: Characterization and Diagnostic Strategies

Familial and Sporadic Porphyria Cutanea Tarda: Characterization and Diagnostic Strategies

Porphyria Cutanea Tarda, Hepatitis C, Uroporphyrinogen Decarboxylase and Mutations of HFE Gene

Hepatoerythropoietic Porphyria and Familial Porphyria Cutanea Tarda in Spanish Patients: G281E Mutation in the Uroporphyrinogen Decarboxylase Gene

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