Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption.

Selective vitamin B(12) malabsorption or Gräsbeck-Imerslund disease (megaloblastic anemia 1) is frequently accompanied by proteinuria. The malabsorption-proteinuric syndrome of Finnish patients is caused by a defect in the multiligand receptor cubilin. We studied the urinary proteins of control subjects and 13 adult patients with three defined cubilin mutations (FM1, FM2, FM3), all diagnosed during childhood and subsequently observed.

Amnionless, essential for mouse gastrulation, is mutated in recessive hereditary megaloblastic anemia.

The amnionless gene, Amn, on mouse chromosome 12 encodes a type I transmembrane protein that is expressed in the extraembryonic visceral layer during gastrulation. Mice homozygous with respect to the amn mutation generated by a transgene insertion have no amnion. The embryos are severely compromised, surviving to the tenth day of gestation but seem to lack the mesodermal layers that normally produce the trunk.