title: The productive gene for alpha-H chain disease protein MAL is highly modified by insertion-deletion processes.
abstract: alpha-H chain diseases (HCD) is a human lymphoproliferative disorder, characterized by the production of truncated alpha-Ig H chains, without associated L chains. In this study, we have analysed the serum protein, the alpha-HCD mRNA and the rearranged alpha-HCD gene from the leukemic cells of a patient (MAL) with alpha-HCD. The abnormal MAL serum Ig consisted of short alpha 1-chains, lacking VH and CH1 domains (only CH2 and CH3 domains were present). The alpha-HCD mRNA (1.2 kb) was shorter than a normal alpha-mRNA (2 kb); the corresponding cDNA had sequences for the leader, a 84-bp sequence of unknown origin and the CH2 and CH3 exons. The establishment of the sequence of the productive alpha-HCD MAL allele revealed two major deletions; that of the VH region as well as that of the CH1 region. The JH region is altered by multiple mutations, small insertions and a duplication of the psi JH3 region. A large insert (INS1), of 360 bp (containing the 84 bp exon found in the cDNA), replaces the deleted VH region. INS1 is non-Ig related and apparently of nongenomic origin. A large second insert (509 bp), is located between the enhancer and the switch region. Insert2 contains repetitive non-Ig-related sequences and a small Ig-related sequence. All these alterations resulted in an abnormal mRNA, which comprises the leader, a 84-bp alien exon derived from INS1 and the CH2 and CH3 exons of the alpha 1-gene.
authors.affiliation: Laboratoire d'Immunochimie et d'Immunopathologie, INSERM U.108, Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Tsapis
authors.forename: M
authors.initials: M
authors.lastname: Bentaboulet
authors.forename: P
authors.initials: P
authors.lastname: Pellet
authors.forename: E
authors.initials: E
authors.lastname: Mihaesco
authors.forename: D
authors.initials: D
authors.lastname: Thierry
authors.forename: M
authors.initials: M
authors.lastname: Seligmann
authors.forename: J C
authors.initials: JC
authors.lastname: Brouet
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D004247:DNA / Q000302:isolation & purification; D004251:DNA Transposable Elements; D004742:Enhancer Elements, Genetic; D005803:Genes, Immunoglobulin; D006362:Heavy Chain Disease / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000302:isolation & purification; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007137:Immunoglobulin alpha-Chains / Q000235:genetics* / Q000302:isolation & purification; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D004251:DNA Transposable Elements; D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D007137:Immunoglobulin alpha-Chains; D009363:Neoplasm Proteins; D004247:DNA