NOVEL POINT MUTATION IN THE UROPORPHYRINOGEN-III SYNTHASE GENE CAUSESCONGENITAL ERYTHROPOIETIC PORPHYRIA OF A JAPANESE FAMILY

The molecular basis of the uroporphyrinogen III synthase (UROIIIS) def iciency was investigated in a member of a Japanese family, This defect in heme biosynthesis is responsible for a rare autosomal recessive di sease: congenital erythropoietic porphyria (CEP) or Gunther's disease, The patient was homozygous for a novel missense mutation: a G to T tr ansition of nucleotide 7 that predicted a valine to phenylalanine subs titution at residue 3 (V3F), The parents were heterozygous for the sam e mutation, The loss of UROIIIS activity was verified by an in vitro a ssay system, The corresponding mutated protein was expressed in Escher ichia coli and no residual activity was observed. Further studies are needed to determine whether the mutations of the UROIIIS gene (UROS) h ave a specific profile in Japan compared to European or American count ries. (C) 1997 Wiley-Liss, Inc.