Affiliation:
1. Laboratoire de Biochimie Medicale et Biologie Moleculaire, Universite de Bordeaux II, France.
Abstract
Congenital erythropoietic porphyria (CEP) is an inherited metabolic disorder resulting from the accumulation of porphyrins because of defective uroporphyrinogen III synthase (UROIIIS). This autosomal recessive disorder is phenotypically heterogeneous with respect to the age of onset and the severity of the symptoms. Different exonic point mutations in the UROIIIS gene have been identified, providing phenotype- genotype correlations in this disease. Severe cases may be treated by bone marrow transplantation and are potential candidates for somatic gene therapy. Epstein-Barr virus-transformed B-cell lines from patients with CEP provide a model system for the disease. We have used retrovirus-mediated expression of UROIIIS to restore enzymatic activity in a B-cell line from a patient. We have also demonstrated the metabolic correction of the disease, ie, porphyrin accumulation into the deficient transduced cells was reduced to the normal level. These data show the potential of gene therapy for this disease.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
39 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Inherited Porphyrias;Emery and Rimoin's Principles and Practice of Medical Genetics and Genomics;2021
2. Inherited Porphyrias;Emery and Rimoin's Principles and Practice of Medical Genetics;2013
3. Metabolic Correction of Congenital Erythropoietic Porphyria with iPSCs Free of Reprogramming Factors;The American Journal of Human Genetics;2012-07
4. Porphyrias;Harper's Textbook of Pediatric Dermatology;2011-05-24
5. Modeling of congenital erythropoietic porphyria by RNA interference: a new tool for preclinical gene therapy evaluation;The Journal of Gene Medicine;2010-06-29