Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene
AUTOR(ES)
Tanner, Stephan M.
FONTE
National Academy of Sciences
RESUMO
Hereditary juvenile megaloblastic anemia due to vitamin B12 (cobalamin) deficiency is caused by intestinal malabsorption of cobalamin. In Imerslund–Gräsbeck syndrome (IGS), cobalamin absorption is completely abolished and not corrected by the administration of intrinsic factor (IF); if untreated, the disease is fatal. Biallelic mutations either in the cubilin (CUBN) or amnionless (AMN) gene cause IGS. In a series of families clinically diagnosed with likely IGS, at least six displayed no evidence of mutations in CUBN or AMN. A genome-wide search for linkage followed by mutational analysis of candidate genes was performed in five of these families. A region in chromosome 11 showed evidence of linkage in four families. The gastric IF (GIF) gene located in this region harbored homozygous nonsense and missense mutations in these four families and in three additional families. The disease in these cases therefore should be classified as hereditary IF deficiency. Clinically, these patients resembled those with typical IGS; radiocobalamin absorption tests had been inconclusive regarding the nature of the defect. In the diagnosis of juvenile cobalamin deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a molecular characterization of the underlying defect and may be the diagnostic method of choice.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=554821Documentos Relacionados
- Hereditary porcine membranoproliferative glomerulonephritis type II is caused by factor H deficiency.
- Intrinsic Factor-mediated Absorption of Cobalamin by Guinea Pig Ileal Cells
- Hereditary defect of cobalamin metabolism (homocystinuria and methylmalonic aciduria) of juvenile onset.
- The molecular basis of hereditary complement factor I deficiency.
- Cobalamin deficiency in elderly patients