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Clinical, Biochemical, and Genetic Study of 11 Patients With Erythropoietic Protoporphyria Including One With Homozygous Disease
Carmen Herrero, MD, PhD;
Jordi To-Figueras, PhD;
Celia Badenas, PhD;
Manuel Méndez, PhD;
Patricia Serrano, MD;
Rafael Enríquez-Salamanca, MD, PhD;
Mario Lecha, MD, PhD
Arch Dermatol. 2007;143(9):1125-1129.
Objective To study the mutations in the ferrochelatase gene (FECH) and the phenotypic expression of erythropoietic protoporphyria (EPP) in a group of Spanish patients.
Design Case series.
Setting University-based hospital.
Patients Eleven unrelated patients with EPP and 19 asymptomatic relatives from 10 families.
Main Outcomes Measures Measurement of protoporphyrin concentration in red blood cells and feces by fluorometry and chromatography. Analysis of the mutations of the FECH gene by single-strand conformation analysis. Expression of mutations in Escherichia coli.
Results FECH gene mutations were found in all 11 patients. Ten were heterozygous and carried the IVS3-48C low-expression allele. Three novel mutations were found: IVS4 + 1delG, 347-351delC, and 130_147dupl 18. One patient did not present the IVS3-48C polymorphism and was found to harbor a novel A185T missense mutation in both alleles. The familial study confirmed a recessive mode of inheritance of the disease. The A185T mutation showed a residual activity 4% of normal when expressed in E coli. This patient presented cutaneous photosensitivity similar to the heterozygous cases, but a higher protoporphyrin accumulation in erythrocytes, microcytic anemia, and early signs of liver engagement. FECH mutations were found in 10 healthy relatives, none of whom carried the low-expression allele. The frequency of the IVS3-48C allele among 180 nonporphyric Spanish individuals was 5.2%.
Conclusions These findings confirm, among a group of Spanish patients, that most cases of EPP result from the coinheritance of IVS3-48C and a mutation in the FECH gene, and also document the existence of patients with mutations in homozygosity that may present a more severe form of the disease.
Author Affiliations: Departments of Dermatology (Drs Herrero, Serrano, and Lecha) and Biochemistry and Molecular Genetics (Drs To-Figueras and Badenas), Hospital Clinic of Barcelona, University of Barcelona, IDIBAPS (Institut d'Investigacions Biomèdiques August Pi i Sunyer), Barcelona, Spain; and Centro de Investigación, Hospital 12 de Octubre, Madrid, Spain (Drs Méndez and Enríquez-Salamanca).
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