An exon 53 frameshift mutation in CUBN abrogates cubam function and causes Imerslund-Grasbeck syndrome in dogs.

ABSTRACT: Cobalamin malabsorption accompanied by selective proteinuria is an autosomal recessive disorder known as Imerslund-Gräsbeck syndrome in humans and was previously described in dogs due to amnionless (AMN) mutations. The resultant vitamin B12 deficiency causes dyshematopoiesis, lethargy, failure to thrive, and life-threatening metabolic disruption in the juvenile period. We studied 3 kindreds of border collies with cobalamin malabsorption and mapped the disease locus in affected dogs to a 2.9Mb region of homozygosity on canine chromosome 2. The region included CUBN, the locus encoding cubilin, a peripheral membrane protein that in concert with AMN forms the functional intrinsic factor-cobalamin receptor expressed in ileum and a multi-ligand receptor in renal proximal tubules. Cobalamin malab

SUBMITTER: Fyfe JC 

PROVIDER: S-EPMC3729882 | biostudies-literature | 2013 Aug

REPOSITORIES: biostudies-literature