Alpha heavy chain disease of patient MAL: structure of the non-functional rearranged α gene translocated on chromosome 9

Publisher Website
Google Scholar
Abstract
Alpha heavy chain diseases (HCD) are lymphoproliferative disorders characterized by the production of truncated α immunoglobulin heavy chain without associated light chains, α HCD MAL is featured by multiple structural alterations of the α1 productive gene and on original t(9;14)(p11;q32) translocation involving the other rearranged α allele. We present here the structure of the der(9) chromosome. Sequence analysis provides evidence that the translocation occurred after local pairing of the two chromosomes mediated by an almost perfect nonameric sequence, followed by a staggered double‐strand break of chromosome 14. This translocation occurred on a V(D)J rearranged locus; unexpectedly, there were a deletion of the 3' part of the VH gene, several insertions of non‐immunoglobulin‐related genes and multiple mutations, i.e. alterations reminiscent of those occurring on the HCD productive genes.