Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism
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Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. / Coelho, David; Kim, Jaeseung C; Miousse, Isabelle R; Fung, Stephen; du Moulin, Marcel; Buers, Insa; Suormala, Terttu; Burda, Patricie; Frapolli, Michele; Stucki, Martin; Nürnberg, Peter; Thiele, Holger; Robenek, Horst; Höhne, Wolfgang; Longo, Nicola; Pasquali, Marzia; Mengel, Eugen; Watkins, David; Shoubridge, Eric A; Majewski, Jacek; Rosenblatt, David S; Fowler, Brian; Rutsch, Frank; Baumgartner, Matthias R.
in: NAT GENET, Jahrgang 44, Nr. 10, 10.2012, S. 1152-5.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism
AU - Coelho, David
AU - Kim, Jaeseung C
AU - Miousse, Isabelle R
AU - Fung, Stephen
AU - du Moulin, Marcel
AU - Buers, Insa
AU - Suormala, Terttu
AU - Burda, Patricie
AU - Frapolli, Michele
AU - Stucki, Martin
AU - Nürnberg, Peter
AU - Thiele, Holger
AU - Robenek, Horst
AU - Höhne, Wolfgang
AU - Longo, Nicola
AU - Pasquali, Marzia
AU - Mengel, Eugen
AU - Watkins, David
AU - Shoubridge, Eric A
AU - Majewski, Jacek
AU - Rosenblatt, David S
AU - Fowler, Brian
AU - Rutsch, Frank
AU - Baumgartner, Matthias R
PY - 2012/10
Y1 - 2012/10
N2 - Inherited disorders of vitamin B12 (cobalamin) have provided important clues to how this vitamin, which is essential for hematological and neurological function, is transported and metabolized. We describe a new disease that results in failure to release vitamin B12 from lysosomes, which mimics the cblF defect caused by LMBRD1 mutations. Using microcell-mediated chromosome transfer and exome sequencing, we identified causal mutations in ABCD4, a gene that codes for an ABC transporter, which was previously thought to have peroxisomal localization and function. Our results show that ABCD4 colocalizes with the lysosomal proteins LAMP1 and LMBD1, the latter of which is deficient in the cblF defect. Furthermore, we show that mutations altering the putative ATPase domain of ABCD4 affect its function, suggesting that the ATPase activity of ABCD4 may be involved in intracellular processing of vitamin B12.
AB - Inherited disorders of vitamin B12 (cobalamin) have provided important clues to how this vitamin, which is essential for hematological and neurological function, is transported and metabolized. We describe a new disease that results in failure to release vitamin B12 from lysosomes, which mimics the cblF defect caused by LMBRD1 mutations. Using microcell-mediated chromosome transfer and exome sequencing, we identified causal mutations in ABCD4, a gene that codes for an ABC transporter, which was previously thought to have peroxisomal localization and function. Our results show that ABCD4 colocalizes with the lysosomal proteins LAMP1 and LMBD1, the latter of which is deficient in the cblF defect. Furthermore, we show that mutations altering the putative ATPase domain of ABCD4 affect its function, suggesting that the ATPase activity of ABCD4 may be involved in intracellular processing of vitamin B12.
KW - ATP-Binding Cassette Transporters
KW - Abnormalities, Multiple
KW - Case-Control Studies
KW - Cells, Cultured
KW - DNA Mutational Analysis
KW - Fibroblasts
KW - Gene Expression
KW - Genes, Recessive
KW - Genetic Association Studies
KW - Humans
KW - Infant, Newborn
KW - Lysosome-Associated Membrane Glycoproteins
KW - Metabolism, Inborn Errors
KW - Mutation
KW - Nucleocytoplasmic Transport Proteins
KW - Protein Structure, Tertiary
KW - Protein Transport
KW - Vitamin B 12
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1038/ng.2386
DO - 10.1038/ng.2386
M3 - SCORING: Journal article
C2 - 22922874
VL - 44
SP - 1152
EP - 1155
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 10
ER -