ĐỘT BIẾN GEN UROPORPHYRINOGEN III COSYNTHASE TRÊN MỘT BÉ GÁI MẮC BỆNH PORPHYRIA TẠO HỒNG CẦU BẨM SINH TẠI VIỆT NAM

Abstract

Background: Congenital erythropoietic porphyria (CEP) arises from an autosomal recessive inherited disorder of the porphyrin metabolism, which leads to the accumulation of uroporphyrinogen I in bone marrow, skin and several other tissues by a deficiency of uroporphyrinogen III cosynthase (UROS). Case report: To describe clinical feature and gene mutation in a patient treated  at National Hospital of Dermatology and Venereology. A five-year-old Vietnamese girl suffering from severe cutaneous photosensitivity with skin fragility, bullous lesions and hypertrichosis on light-exposed areas. We described for the first time a mutation in the UROS gene in a Southeast Asian patient and a molecular diagnosis for the identification of clinically asymptomatic heterozygous mutation carriers and families with CEP. To clarify the first molecular basis of Vietnamese family, identification of UROS mutation, and measurement activity of uroporphyrinogen III cosynthase in a patient with CEP were performed. A missense mutation in the UROS gene was identified as a transversion of G to T at nucleotide 11,776, resulting in a substitution of valine by phenylalanine at codon 3 of exon 2. The patient showed a homozygous mutant profile, and the heterozygous state was observed in the parents. The activity of mutated UROS expressed in Escherichia coli was less than 16.1% that of the control, indicating that the markedly reduced activity of UROS from genetic mutation is responsible for CEP. Conclusions: The mutational analysis of gene causing CEP is important in the patient’s disease management. Genetic counseling of the family and prenatal diagnosis is strongly recommended in this rare disease.