We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B<sub>12</sub> metabolism.
- Authors
Rutsch, Frank; Gailus, Susann; Miousse, Isabelle R.; Suormala, Terttu; Sagné, Corinne; Toliat, Mohammad Reza; Nürnberg, Gudrun; Wittkampf, Tanja; Buers, Insa; Sharifi, Azita; Stucki, Martin; Becker, Christian; Baumgartner, Matthias; Robenek, Horst; Marquardt, Thorsten; Höhne, Wolfgang; Gasnier, Bruno; Rosenblatt, David S.; Fowler, Brian; Nürnberg, Peter
- Abstract
Vitamin B12 (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 B12 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.
- Subjects
VITAMIN B12; METABOLISM; AMINO acids; FATTY acids; MEMBRANE proteins; FIBROBLASTS; GENETIC mutation
- Publication
Nature Genetics, 2009, Vol 41, Issue 2, p234
- ISSN
1061-4036
- Publication type
Article
- DOI
10.1038/ng.294