A MUTATION IN THE CERULOPLASMIN GENE IS ASSOCIATED WITH SYSTEMIC HEMOSIDEROSIS IN HUMANS

We identified a mutation in the ceruloplasmin (Cp) gene in a Japanese family with aceruloplasminemia, some of whose members showed extrapyra midal disorders, cerebellar ataxia, and diabetes mellitus. A post-mort em study of the proband revealed excessive iron deposition mainly in t he brain, liver and pancreas. The G to A transition at the splice acce ptor site introduces a premature termination codon at the amino acid p osition 991 by defective splicing, thereby truncating the carboxyl ter minus of Cp in affected individuals. We conclude that the mutation in the Cp gene is associated with systemic hemosiderosis in humans.