DETECTION OF THE HETEROZYGOUS CARRIER OF THE WILSON'S DISEASE GENE*

In his original monograph, Wilson described the disease which is now named for him as "... familial, in the sense that frequently more than one member of a family is affected with it, but... not hereditary " (1). Subsequent studies (2-4) have indicated, however, that the disease is hereditary and is transmitted in autosomal recessive fashion by parents who never develop the illness. This implies both that Wilson's disease appears in those subjects who are homozygous for the "Wil-son's disease gene " and that each parent of such a subject must be a heterozygote who possesses one of these abnormal genes and one of its normal alleles. We have chosen to designate the geno-types of patients, heterozygotes, and normal indi-viduals, respectively, as cc, Cc, and CC. The patient in whom Wilson's disease is, or will be, clinically manifest exhibits four abnor-malities of copper metabolism: 1) a persistent de-ficiency or absence of normal ceruloplasmins, the blue, plasma copper-proteins (3, 5, 6); 2) an in-creased concentration of loosely bound, non-ceru-loplasmin copper in serum (6, 7); 3) an increased copper content of many organs and tissues (6, 8-13); and 4) an increased excretion of copper i