TY - JOUR
T1 - Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1
AU - Aminoff, Maria
AU - Carter, Jo Ellen
AU - Chadwick, Robert B.
AU - Johnson, Cheryl
AU - Gräsbeck, Ralph
AU - Abdelaal, Mohamed A.
AU - Broch, Harald
AU - Jenner, Lasse B.
AU - Verroust, Pierre J.
AU - Moestrup, Soeren K.
AU - De La Chapelle, Albert
AU - Krahe, Ralf
N1 - Funding Information:
We thank the patients and their families for continued cooperation; S. Lindh for assistance with sample collection; L. Aaltonen and P. Peltomäki for providing control DNA samples; F. Wright and X. Gao for statistical advice and support; and K. Virtaneva and C. Plass for critical reading of the manuscript. M.A. and A.d.l.C. were supported by the Ulla Hjelt Fund, Liv och Hälsa and the Academy of Finland. This study was supported in part by grant P30 CA16058, National Cancer Institute.
PY - 1999/3
Y1 - 1999/3
N2 - 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.
AB - 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.
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U2 - 10.1038/6831
DO - 10.1038/6831
M3 - Article
C2 - 10080186
AN - SCOPUS:0033051889
SN - 1061-4036
VL - 21
SP - 309
EP - 313
JO - Nature Genetics
JF - Nature Genetics
IS - 3
ER -