Back to Search
Start Over
Mutations in the mu heavy-chain gene in patients with agammaglobulinemia.
- Source :
-
The New England journal of medicine [N Engl J Med] 1996 Nov 14; Vol. 335 (20), pp. 1486-93. - Publication Year :
- 1996
-
Abstract
- Background: Most patients with congenital hypogammaglobulinemia and absent B cells are males with X-linked agammaglobulinemia, which is caused by mutations in the gene for Bruton's tyrosine kinase (Btk); however, there are females with a similar disorder who do not have mutations in this gene. We studied two families with autosomal recessive defects in B-cell development and patients with presumed X-linked agammaglobulinemia who did not have mutations in Btk.<br />Methods: A series of candidate genes that encode proteins involved in B-cell signal-transduction pathways were analyzed by linkage studies and mutation screening.<br />Results: Four different mutations were identified in the mu heavy-chain gene on chromosome 14. In one family, there was a homozygous 75-to-100-kb deletion that included D-region genes, J-region genes, and the mu constant-region gene. In a second family, there was a homozygous base-pair substitution in the alternative splice site of the mu heavy-chain gene. This mutation would inhibit production of the membrane form of the mu chain and produce an amino acid substitution in the secreted form. In addition, a patient previously thought to have X-linked agammaglobulinemia was found to have an amino acid substitution on one chromosome at an invariant cysteine that is required for the intrachain disulfide bond and, on the other chromosome, a large deletion that included the immunoglobulin locus.<br />Conclusions: Defects in the mu heavy-chain gene are a cause of agammaglobulinemia in humans. This implies that an intact membrane-bound mu chain is essential for B-cell development.
Details
- Language :
- English
- ISSN :
- 0028-4793
- Volume :
- 335
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 8890099
- Full Text :
- https://doi.org/10.1056/NEJM199611143352003