Molecular analysis of the IGHA and MHC class III region genes in one family with IgA and C4 deficiencies.
We report molecular studies in 2 IgA-deficient persons. One of them had an unusual association with an acute lymphoblastic leukaemia; his sister was also IgA deficient and shared an HLA haplotype and a complotype known to be associated to IgA deficiencies. The 2 IgA-deficient siblings also had low C4 serum levels due to C4A*Q0 allele. We showed that both defects were transmitted independently in the family. Molecular analysis revealed no major structural defects of the IGHA coding and switch regions, whereas a broad C4A-21-OHA deletion was responsible for the C4A*Q0 phenotype. These results confirm previous data showing that IgA deficiencies seem to be, in most cases, a regulatory defect rather than a structural defect of the coding IGHA region itself. These data were further supported by another molecular study in a patient with a recurrent Landry-Guillain-Barre syndrome who showed total absence of serum IgA and sIgA+B cells with no major structural defect of the IGHA region.
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Laboratoire d'Immunogénétique Moléculaire, URA CNRS 1191, Université Montpellier II, France.
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D000293:Adolescent; D015139:Blotting, Southern; D003181:Complement C4 / Q000172:deficiency* / Q000235:genetics; D015342:DNA Probes; D004406:Dysgammaglobulinemia / Q000235:genetics*; D015698:Genomic Library; D006801:Humans; D017098:IgA Deficiency; D007070:Immunoglobulin A / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007134:Immunoglobulin Switch Region / Q000235:genetics; D008285:Major Histocompatibility Complex / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D003181:Complement C4; D015342:DNA Probes; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains