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Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism

Rutsch, Frank and Gailus, Susann and Miousse, Isabelle R. and Suormala, Terttu and Sagné, Corinne and Toliat, Mohammad Reza and Nürnberg, Gudrun and Wittkampf, Tanja and Buers, Insa and Sharifi, Azita and Stucki, Martin and Becker, Christian and Baumgartner, Matthias and Robenek, Horst and Marquardt, Thorsten and Höhne, Wolfgang and Gasnier, Bruno and Rosenblatt, David S. and Fowler, Brian and Nürnberg, Peter. (2009) Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism. Nature genetics, Vol. 41, H. 2. pp. 234-239.

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Official URL: http://edoc.unibas.ch/dok/A5253668

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Abstract

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.
Faculties and Departments:03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Ehemalige Einheiten Pädiatrie (UKBB) > Labor (Fowler)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Ehemalige Einheiten Pädiatrie (UKBB) > Labor (Fowler)
03 Faculty of Medicine > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Pädiatrie (Frey)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Kinder- und Jugendheilkunde (Klinik) > Kinder- und Jugendheilkunde (UKBB) > Pädiatrie (Frey)
UniBasel Contributors:Fowler, Brian
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Nature Publ
ISSN:1061-4036
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:45
Deposited On:22 Mar 2012 13:36

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