Congenital Erythropoietic Porphyria: Report of a Novel Mutation with Absence of Clinical Manifestations in a Homozygous Mutant Sibling
| Autor: | Cécile Ged, Hala Mégarbané, Eliane Chouery, André Mégarbané, Magalie Lalanne, Hubert de Verneuil |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
Male Porphyria Erythropoietic Uroporphyrinogen III synthase Mutant Congenital erythropoietic porphyria Dermatology porphyrins medicine.disease_cause Biochemistry DNA studies medicine Humans Child Molecular Biology Gene Genetics CEP Mutation Base Sequence incomplete penetrance biology Siblings Homozygote uroporphyrinogen III synthase Cell Biology medicine.disease Uroporphyrinogen III Synthetase Penetrance Phenotype Arabs Pedigree Erythropoietic porphyria biology.protein Female |
| Zdroj: | Journal of Investigative Dermatology. 123:589-591 |
| ISSN: | 0022-202X |
| DOI: | 10.1111/j.0022-202x.2004.23401.x |
| Popis: | In a Palestinian family, four siblings were shown to express typical and severe congenital erythropoietic porphyria (CEP). A new mutation of the uroporphyrinogen III synthase (UROS) gene was evidenced by systematic sequencing of the UROS gene: the substitution of serine by proline at the amino acid residue 47 (S47P) was present at the homozygous state in the four patients. The mother was heterozygous, the father was not examined. Surprisingly, in one unaffected sister, UROS activity was markedly deficient and UROS gene analysis showed a homozygous mutant profile. The deleterious role of the mutant S47P protein on UROS activity was demonstrated by prokaryotic expression. This observation is the first report of a healthy status associated with homozygosity for a mutation of UROS gene in a severely affected family. We then draw hypotheses to explain the protective phenotype in the homozygous healthy subject. |
| Databáze: | OpenAIRE |
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