IDENTIFICATION OF A NOVEL MUTATION OF THE CPO GENE IN A JAPANESE HEREDITARY COPROPORPHYRIA FAMILY

Hereditary coproporphyria (HCP) is an autosomal dominant disease chara cterized by a deficiency of coproporphyrinogen oxidase (CPO) caused by a mutation in the CPO gene. Only 11 mutations of the gene have been r eported in HCP patients. We report another mutation in a Japanese fami ly. Polymerase chain reaction-single strand conformational polymorphis m and direct sequence analyses demonstrated a C to T substitution in e xon 1 of the CPO gene at nucleotide position 85, which lies in the put ative presequence for targeting to mitochondria. This mutation changes the codon for glutamine to a termination codon at amino acid position 29, MaeI restriction analysis showed two other carriers in the family . The C-T mutation is located within a recently proposed putative alte rnative translation initiation codon (TIC-1), supporting that TIC-1 is the real TIC rather than TIC-2. (C) 1998 Wiley-Liss, Inc.