N-and C-terminal Sequences of a Heavy Chain Disease Protein and its Genetic Implications

A VARIANT of myeloma has been described1,2; it is known as heavy chain disease, and is characterized by the presence of a homogeneous serum and urinary protein bearing only the antigenic determinants associated with the heavy or γ-chain of human IgG immunoglobulin. Five such cases have been described, but the protein of two patients, Zu1and Cr2,3, have been more extensively investigated because of the availability of material and appear to share common structural features. The proteins are symmetrical dimers, stabilized by disulphide bonds, with molecular weights in the range of 50,000–55,000. Peptide maps reveal they contain the Fc portion of the heavy chain as a chief structural unit3. This conclusion is supported by the content of carbohydrate3, the presence of Gm specificities4, and biological activities5,6of these proteins, properties also attributed to the C-terminal half of the heavy chain.