Report of a cubilin deficient patient

Background Cubilin is an important receptor involved in intestinal absorption of vitamin B 12 and reabsorption of proteins from the glomerular ultrafiltrate. Murine studies furthermore suggest that both cubilin and the receptor partner amnionless are essential for normal embryonic development. Cubilin function is affected in Imerslund‐Gräsbeck syndrome (IGS) patients. IGS is a rare, autosomal recessive disorder characterized by a selective, intestinal, intrinsic factor‐vitamin B 12 malabsorption and is often accompanied by an additional proteinuria. Aim To investigate the role of cubilin in renal protein handling in a patient with cubilin deficiency. Results A novel homozygous null mutation of the CUBN gene was identified in a conserved donor splice site in a male IGS patient. No cubilin was detected in a renal biopsy and an abnormal, cytoplasmic distribution of the receptor partner amnionless was also observed. Immunoblotting of patient urine, accordingly, showed selective tubular proteinuria with increased excretion of cubilin ligands. Conclusions This clearly demonstrates a central role of cubilin in handling of filtered proteins in the human kidney and demonstrates the interdependent relationship of cubilin and amnionless in man. This patient furthermore, presented with no additional developmental abnormalities suggesting that cubilin is not essential for human embryonic development.