Genomic alterations in a case of α heavy chain disease leading to the generation of composite exons from the jh region

✍ Scribed by Martine Bentaboulet; Edith Mihaesco; Marie-Claude Gendron; Jean-Claude Brouet; Andreas Tsapis

• Publisher: John Wiley and Sons
• Year: 1989
• Tongue: English
• Weight: 570 KB
• Volume: 19
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830191119

✦ Synopsis

Genomic alterations in a case of a heavy chain disease leading to the generation of composite exons from the J H region

Human a heavy chain disease (HCD) is characterized by the presence in patient's serum of a short Ig a chain devoid of light chains. We analyzed the serum protein, the aHCD mRNA and the productive rearranged H chain gene from the leukemic cells of a new case (YAO) of aHCD. The abnormal YAO a1 Ig was devoid of VH and C H I domains and started at the beginning of the hinge region. The aHCD mRNA was shorter than normal a mRNA and the cDNA prepared from YAO mRNA encoded a leader sequence, an insert of 70 nucleotides and the cH2 and cH3 exons. The origin of the inserted sequence was assessed by cloning and sequence analysis of the a1 productive gene. It started with a leader exon, a leader-VH intron and the first 11 bp of aVH exon.Then theVH region was deleted and replaced by a 1Pnucleotide sequence that turned out t o correspond to the 3' part of a modified J H ~ exon. It was followed by a 221-bp sequence homologous to the J ~5 -v J H ~ intron and by an inserted sequence of unknown origin. The 3' part of this insertion and the remnant of a J H ~ exon delineated a third exon that was followed by a relatively conserved J ~6 -c ~ intron.These two composite exons were flanked by splicing sites and accounted for the 70-nucleotide insert of the cDNA. The genomic nucleotide sequence also revealed a large deletion in the switch CHI region which eliminated normal splicing sites and resulted in splicing of the third exon directly to the C"2 exon.