Molecular analysis of the T17 immunoglobulin CH multigene deletion (del A1-GP-G2-G4-E)

In the human, the order of the immunoglobulin heavy chain constant region (Ig CH) genes is the following: 5'-M-D-G3-G1-EP1-A1-GP-G2-G4-E-A2-3'. Extensive multigene deletions have been described in the Ig CH locus, some of these encompassing up to 160 kb. To date six different multigene deletion haplotypes have been identified, designated I to VI according to the chronological order of their being found: deletion I (del G1-EP1-A1-GP-G2-G4), II (del EP1-A1-GP), III (del A1-GP-G2-G4-E), IV (del EP1-A1-GP-G2-G4), V (del GP-G2-G4-E-A2), VI (del G1-EP1-A1-GP-G2). Individuals were found either homozygous for one type of deletion or heterozygous for two different deletions, mainly (17 cases out of 18) in the Mediterranean area. So far, deletions I and II have been found in Tunisia, deletions III, IV and V in Italy, and deletion VI in Sweden. In this paper, we show that a Tunisian, T17, previously reported as being homozygous for a deletion of type IV, is, in fact, homozygous for a deletion that encompasses A1-GP-G2-G4-E. Therefore T17 is the first case of a deletion of type III reported in the Tunisian population. Molecular analysis demonstrates that the T17 deletion occurred between highly homologous regions located downstream of IGHEP1 and IGHE, respectively. In contrast to the EZZ deletion, the recombination occurred near or in the switch regions, since the homologous regions involved in the deletion extend over 4.5 kb of DNA and encompass the I alpha 1-S alpha 1 and I alpha 2-S alpha 2 regions, respectively.