Document Detail

Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism.
MedLine Citation:
PMID:  19136951     Owner:  NLM     Status:  MEDLINE    
Vitamin B(12) (cobalamin) is essential in animals for metabolism of branched chain amino acids and odd chain fatty acids, and for remethylation of homocysteine to methionine. In the cblF inborn error of vitamin B(12) metabolism, free vitamin accumulates in lysosomes, thus hindering its conversion to cofactors. Using homozygosity mapping in 12 unrelated cblF individuals and microcell-mediated chromosome transfer, we identified a candidate gene on chromosome 6q13, LMBRD1, encoding LMBD1, a lysosomal membrane protein with homology to lipocalin membrane receptor LIMR. We identified five different frameshift mutations in LMBRD1 resulting in loss of LMBD1 function, with 18 of the 24 disease chromosomes carrying the same mutation embedded in a common 1.34-Mb haplotype. Transfection of fibroblasts of individuals with cblF with wild-type LMBD1 rescued cobalamin coenzyme synthesis and function. This work identifies LMBRD1 as the gene underlying the cblF defect of cobalamin metabolism and suggests that LMBD1 is a lysosomal membrane exporter for cobalamin.
Frank Rutsch; Susann Gailus; Isabelle R Miousse; Terttu Suormala; Corinne Sagné; Mohammad Reza Toliat; Gudrun Nürnberg; Tanja Wittkampf; Insa Buers; Azita Sharifi; Martin Stucki; Christian Becker; Matthias Baumgartner; Horst Robenek; Thorsten Marquardt; Wolfgang Höhne; Bruno Gasnier; David S Rosenblatt; Brian Fowler; Peter Nürnberg
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-01-11
Journal Detail:
Title:  Nature genetics     Volume:  41     ISSN:  1546-1718     ISO Abbreviation:  Nat. Genet.     Publication Date:  2009 Feb 
Date Detail:
Created Date:  2009-01-28     Completed Date:  2009-02-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9216904     Medline TA:  Nat Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  234-9     Citation Subset:  IM    
Department of General Pediatrics, Münster University Children's Hospital, Albert-Schweitzer-Strasse 33, D-48149 Münster, Germany.
Data Bank Information
Bank Name/Acc. No.:
RefSeq/NP_060583;  NP_071903
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MeSH Terms
Chromosome Deletion
Chromosome Mapping
Chromosomes, Human, Pair 6
Hela Cells
Hyperhomocysteinemia / complications*,  genetics
Lysosome-Associated Membrane Glycoproteins / metabolism
Membrane Transport Proteins / deficiency*,  genetics,  metabolism
Methylmalonic Acid / metabolism*,  urine
Nucleocytoplasmic Transport Proteins / genetics,  metabolism,  physiology
Polymorphism, Genetic
Proteins / genetics*,  isolation & purification,  metabolism
Tissue Distribution
Transcobalamins / genetics*,  isolation & purification,  metabolism
Vitamin B 12 / metabolism*
Vitamin B 12 Deficiency / etiology,  genetics*,  metabolism
Reg. No./Substance:
0/LAMP1 protein, human; 0/LMBRD1 protein, human; 0/Lysosome-Associated Membrane Glycoproteins; 0/Membrane Transport Proteins; 0/Nucleocytoplasmic Transport Proteins; 0/Proteins; 0/Transcobalamins; 0/lysosomal proteins; 516-05-2/Methylmalonic Acid; 68-19-9/Vitamin B 12

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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