Description of a New Mutation in Hepatoerythropoietic Porphyria and Prenatal Exclusion of a Homozygous Fetus

Ged, Cécile; Ozalla, Dolores; Herrero, Carmen; Lecha, M.; Méndez, Manuel; Verneuil, Hubert de; Mascaró, José M.

doi:10.1001/archderm.138.7.957

Cited by 21 publications

(16 citation statements)

References 22 publications

(9 reference statements)

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“…The F46L mutation, found in two independent probands of our series, had been previously reported in patients with HEP and also in a PCT patient from Chile (21, 24, 25). One study reported an HEP patient with a unique urinary excretion pattern with a predominance of pentacarboxylated porphyrins (25).…”

Section: Discussionsupporting

confidence: 77%

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Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

et al. 2009

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Porphyria cutanea tarda (PCT) arises from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). Both genetic and environmental factors interplay in the precipitation of clinically overt PCT, but these factors may vary between different geographic areas. Decreased activity of UROD in erythrocytes was used to identify patients with UROD mutations among a group of 130 Spanish PCT patients. Nineteen patients (14.6%) were found to harbor a mutation in the UROD gene. Eight mutations were novel: M1I, 5del10, A22V, D79N, F84I, Q116X, T141I and Y182C. Five others were previously described: F46L, V134Q, R142Q, P150L and E218G. The new missense mutations and P150L were expressed in Escherichia coli. D79N and P150L resulted in proteins that were localized to inclusion bodies. The other mutations produced recombinant proteins that were purified and showed reduced activity (range: 2.3–73.2% of wild type). These single amino acid changes were predicted to produce complex structural alterations and/or reduced stability of the enzyme. Screening of relatives of the probands showed that 37.5% of mutation carriers demonstrated increased urinary porphyrins. This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.

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Section: Discussionsupporting

confidence: 77%

“…One study reported the existence of an HEP pedigree member who was heterozygous for the F46L allele and presented a normal erythrocyte UROD activity (24). …”

Section: Discussionmentioning

confidence: 99%

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

et al. 2009

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“…The mutations consisted of five missense mutations and one frameshift mutation. Whereas three of these mutations are novel ones, the other three have been reported previously by other groups (8,14,20). The likelihood of the novel missense mutations in causing disease was demonstrated by in vitro expression studies.…”

Section: Introductionsupporting

confidence: 62%

The molecular basis of porphyria cutanea tarda in Chile: Identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene

Poblete‐Gutiérrez

Méndez

Wiederholt

et al. 2004

Experimental Dermatology

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The porphyrias are heterogeneous disorders arising from predominantly inherited catalytic deficiencies of specific enzymes in heme biosynthesis. Porphyria cutanea tarda (PCT) results from a decreased activity of uroporphyrinogen decarboxylase, the fifth enzyme in heme biosynthesis. The disorder represents the only porphyria that is not exclusively inherited monogenetically. In PCT, at least two different types can be distinguished: acquired/sporadic (type I) PCT, in which the enzymatic deficiency is limited to the liver and inherited/familial (type II) PCT, which is inherited as an autosomal dominant trait with a decrease of enzymatic activity in all tissues. In an effort to characterize the molecular basis of PCT in Chile, we identified eight mutations in 18 previously unclassified PCT families by polymerase chain reaction, heteroduplex analysis, and automated sequencing. To study the role of these mutations in disease causality, in vitro expression of all novel missense mutations was studied. Our results indicate that the frequency of familial PCT in Chile is approximately 50%, thus, to our knowledge, representing the highest incidence of familial PCT reported to date. The data further emphasize the molecular heterogeneity in type II PCT and demonstrate the advantages of molecular genetic techniques as a diagnostic tool and in the detection of clinically asymptomatic mutation carriers.

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“…32,34 To date, 15 missense mutations, 2 deletions, and 1 nonsense mutation have been reported in HEP. 3,5,17,18,21,25,26,29,30,32,33,34 Homozygosity for the F46L missense mutation causes relatively mild HEP, 29,30 as may be true of the novel V166A mutation in our family. In contrast, mutations that abolish UROD activity, like the 645del1053ins10 lesion in our family, are only compatible with life when the individual's other UROD allele encodes residual enzymatic activity.…”

Section: Commentmentioning

confidence: 56%

“…2,6-9,11-16,19-24,26-34 Spontaneous improvement of acute photosensitivity during later childhood, but persistent skin fragility, has been described. 8,11,29,33 Other patients have presented in the second or third decade of life with mild skin fragility or photodistributed annular plaques. 26,28,30,33 Photomutilation can result in considerable morbidity in patients with HEP via impaired function of the hands and facial disfigurement, making photoprotection essential.…”

Section: Commentmentioning

confidence: 99%

Hepatoerythropoietic Porphyria Misdiagnosed as Child Abuse

Cantatore-Francis

Cohen‐Pfeffer²,

Balwani³

et al. 2010

Arch Dermatol

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Background: Hepatoerythropoietic porphyria (HEP) is a rare autosomal recessive disorder resulting from the markedly deficient, but not absent, activity of the heme biosynthetic enzyme uroporphyrinogen decarboxylase (UROD). The disorder typically manifests during infancy or early childhood with extreme photosensitivity, skin fragility in sun-exposed areas, hypertrichosis, erythrodontia, and pink urine.Observations: Three siblings, offspring of parents of Puerto Rican and Dominican descent, had with excessive scarring on the face and dorsal aspect of the forearms, which initially led to the erroneous suspicion of child abuse. Although these lesions were photodistributed, overt photosensitivity had not been observed, with the exception of a single episode of blistering and ony-

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Description of a New Mutation in Hepatoerythropoietic Porphyria and Prenatal Exclusion of a Homozygous Fetus

Cited by 21 publications

References 22 publications

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

The molecular basis of porphyria cutanea tarda in Chile: Identification and functional characterization of mutations in the uroporphyrinogen decarboxylase gene

Hepatoerythropoietic Porphyria Misdiagnosed as Child Abuse

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