A pre-translational defect in a case of human μ heavy chain disease

Abstract

A patient (BW) was studied with Mu heavy chain disease (μHCD) in whom a leukemic B-cell clone secreted a shortened monoclonal μ chain without associated light chain. The cells did, however, produce a normal-sized k light chain that was detected as urinary Bence-Jones protein. The cytoplasmic and secreted monomeric μ chain had an approximate mol. wt of 58,000. Radiochemical sequence analysis of the biosynthetically labelled μ chain revealed a protein that lacked the entire variable region. The sequence initiated at amino acid position 5 within the first constant region domain (CH 1) of C μ The primary in vitro translation product, the cytoplasmic and secreted proteins were all similarly truncated, thereby excluding extensive postsynthetic degradation. The μRNA, that directed the synthesis of the truncated μ protein, was about 350 bp smaller than the normal μRNA. Furthermore, by primer extension analysis it was possible to localize this deletion in the μRNA to a region 5' of CH 1 Thus, a defect at the level of Ig gene structure/assembly that deletes coding information or results in aberrant RNA processing must be responsible for the truncated μHCD protein BW.