title: Molecular study of proteinuria in patients treated with B₁₂ supplements: do not forget megaloblastic anemia type 1.
abstract: OBJECTIVE
  Current consensus supports the notion that proteinuria is a marker of renal disease with prognostic implications. Whereas most chronic kidney disease patients with proteinuria would often require antiproteinuric agents, there are some exceptions. Megaloblastic anemia type 1 (MGA1) is characterized by megaloblastic anemia due to congenital selective vitamin B(12) malabsorption and proteinuria. In the present study, we describe 2 Israeli Jewish patients with MGA1 and isolated proteinuria.
  
  
  METHODS
  Because of their origin, the patients were screened for the presence of the already studied Tunisian AMN mutation, by direct sequencing the corresponding region from genomic DNA. PCR products were purified and sequenced.
  
  
  RESULTS
  Genomic DNA sequencing of the AMN gene of both patients confirmed that the acceptor splice site in intron 3 was changed from CAG to CGG (208-2A→G).
  
  
  CONCLUSIONS
  We determined the molecular basis of MGA1 in both patients and discuss the involvement of the cubilin/AMN complex in this pathology and its role in the development of the proteinuria. We also discuss the questionable significance of antiproteinuric treatment for these patients.
authors.affiliation: Nephrology and Hypertension Institute, Department of Medicine, Tel Aviv University, Sackler School of Medicine, Chaim Sheba Medical Center, Tel Hashomer, Israel. lironomy@gmail.com
authors.forename: Nomy
authors.initials: N
authors.lastname: Levin-Iaina
authors.forename: Dganit
authors.initials: D
authors.lastname: Dinour
authors.forename: Gabriel
authors.initials: G
authors.lastname: Morduchowicz
authors.forename: Liat
authors.initials: L
authors.lastname: Ganon
authors.forename: Eli J
authors.initials: EJ
authors.lastname: Holtzman
mesh_terms: D000749:Anemia, Megaloblastic / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics; D006801:Humans; D008286:Malabsorption Syndromes / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011507:Proteinuria / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000175:diagnosis* / Q000188:drug therapy / Q000235:genetics*
chemical_list: C484714:AMN protein, human; D008565:Membrane Proteins; D011506:Proteins; D014805:Vitamin B 12