Biochemical and molecular diagnosis of erythropoietic protoporphyria in an Ashkenazi Jewish family
| Autor: | Nili Schoenfeld, R. Mamet, Xiaoye Schneider-Yin, Elisabeth I. Minder |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Erythrocytes Heredity Adolescent Offspring Porphyria Erythropoietic Population DNA Mutational Analysis Protoporphyrins chemistry.chemical_compound Young Adult Genotype Genetics medicine Humans Genetic Predisposition to Disease Photosensitivity Disorders Allele education Genetics (clinical) education.field_of_study biology business.industry Ferrochelatase medicine.disease Prognosis Pedigree Porphyria Phenotype chemistry Jews Immunology Mutation biology.protein Protoporphyrin Female Erythropoietic protoporphyria business Biomarkers |
| Popis: | Summary: Erythropoietic protoporphyria (EPP) is a rare hereditary disorder due to a partial deficiency of ferrochelatase (FECH). The genotype of EPP patients features a mutation on one allele of the FECH gene and a common hypomorphic FECH IVS3-48c on the other allele (M/c). The resulting enzyme activity in patients is ∼35% of that in normal individuals. Ferrochelatase deficiency results in the accumulation of protoporphyrin in the skin, which is responsible for the clinical symptom of cutaneous photosensitivity in patients. In this study, we report the identification of a novel FECH mutation delT23 in an 11-member EPP family of Jewish origin. Two EPP siblings shared an identical genotype of delT23/IVS3-48c (M/c). They were both photosensitive and showed highly increased erythrocyte protoporphyrin. The genotype of the patients' mother, who did not present with any EPP clinical symptoms, was delT23/IVS3-48t (M/t). The patients' father, an offspring of consanguineous parents, was homozygous IVS3-48 c/c. He exhibited a mild photosensitivity, and an increase of 4-fold in erythrocyte protoporphyrin. His FECH mRNA amount was 71% of that of genotype t/t. It is the first reported case of an individual with c/c genotype who exhibits both biochemical and clinical indications of EPP. These results suggest that IVS3-48c is a functional variant of ferrochelatase. The clinical symptoms and biochemical abnormalities in the patients' father could be the result of an interaction between genetic and environmental factors. In addition, the frequency of IVS3-48c in the Ashkenazi Jewish population was estimated at 8%, which is similar to that in the European populations |
| Databáze: | OpenAIRE |
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