1. Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.
- Author
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Aminoff M, Carter JE, Chadwick RB, Johnson C, Gräsbeck R, Abdelaal MA, Broch H, Jenner LB, Verroust PJ, Moestrup SK, de la Chapelle A, and Krahe R
- Subjects
- Amino Acid Sequence, Anemia, Megaloblastic urine, Base Sequence, Blotting, Southern, Blotting, Western, Contig Mapping, Finland, Haplotypes, Homozygote, Humans, Linkage Disequilibrium, Microsatellite Repeats, Molecular Sequence Data, Norway, Physical Chromosome Mapping, Polymorphism, Genetic, Receptors, Cell Surface analysis, Reverse Transcriptase Polymerase Chain Reaction, Saudi Arabia, Urine chemistry, Anemia, Megaloblastic genetics, Mutation, Receptors, Cell Surface genetics
- Abstract
Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.
- Published
- 1999
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