Abstract | UNLABELLED:
Erythropoietic protoporphyria (EPP, MIM 177000) is an inherited disorder caused by a partial deficiency of ferrochelatase (FECH) which catalyses the chelation of iron into protoporphyrin to form haem. The majority of EPP patients experience solely a painful photosensitivity whereas a small number of them develop liver complications due to the accumulation of excessive amount of protoporphyrin in the liver. EPP is considered to be an autosomal dominant disorder, however, with a low clinical penetrance. To date, a total of 65 different mutations have been identified in the FECH gene of EPP patients. Among the 89 EPP patients who carry a "null allele" mutation which results in the formation of a truncated protein, 18 of them developed EPP-related liver complications. None of the 16 missense mutations identified among 19 patients on the other hand, have been associated with liver disease (P = 0.038). The allelic constellation of an overt patient consists of a mutated FECH allele and a "low expressed" normal allele and that of an asymptomatic carrier, a combination of a mutated and a normally expressed FECH allele. The identification of the "low expressed" allele is facilitated by haplotype analysis using two single nucleotide polymorphisms, -251 A/G in the promoter region and IVS1-23C/T. At the current time when only partially effective therapies are available, the disclosures of both "null allele" and the "low expression" mechanisms will improve patient management. CONCLUSION: While covering the important clinical aspect of erythropoietic protoporphyria, this article emphasises the latest achievements in the molecular genetics of the disorder.
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Authors | X Schneider-Yin, L Gouya, A Meier-Weinand, J C Deybach, E I Minder |
Journal | European journal of pediatrics
(Eur J Pediatr)
Vol. 159
Issue 10
Pg. 719-25
(Oct 2000)
ISSN: 0340-6199 [Print] Germany |
PMID | 11039124
(Publication Type: Journal Article, Review)
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Chemical References |
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Topics |
- Alleles
- Ferrochelatase
(metabolism)
- Genetic Predisposition to Disease
- Heterozygote
- Humans
- Liver Diseases
(enzymology, genetics)
- Lymphocytes
(enzymology)
- Mutation
- Phenotype
- Photosensitivity Disorders
(enzymology, etiology, prevention & control)
- Polymorphism, Genetic
- Porphyria, Hepatoerythropoietic
(complications, diagnosis, genetics)
- Protoporphyria, Erythropoietic
- Switzerland
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