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A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient

Gailus, Susann and Suormala, Terttu and Malerczyk-Aktas, Ayse Gül and Toliat, Mohammad R. and Wittkampf, Tanja and Stucki, Martin and Nürnberg, Peter and Fowler, Brian and Hennermann, Julia B. and Rutsch, Frank. (2010) A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient. Journal of Inherited Metabolic Disease, Vol. 33, no. 1. pp. 17-24.

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Official URL: http://edoc.unibas.ch/dok/A6004311

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Abstract

In the cblF defect of vitamin B(12) (cobalamin) metabolism, cobalamin is trapped in lysosomes. Consequently, cobalamin coenzyme synthesis is blocked, and cofactors for methionine synthase and methylmalonyl-coenzyme A (CoA) mutase are deficient. We recently identified LMBRD1 as the causative gene located on chromosome 6q13 and showed that 18 out of 24 alleles in unrelated patients carried the deletion c.1056delG (p.L352fsX18) (Rutsch et al. (Nat Genet 41:234-239, 2009). LMBRD1 encodes the lysosomal membrane protein LMBD1, which presumably facilitates lysosomal cobalamin export. Our patient is the second child of consanguineous Turkish parents. He presented on the second day of life with cerebral seizures due to intraventricular hemorrhage. Plasma homocysteine and urinary methylmalonic acid levels were elevated, and serum cobalamin level was decreased. Synthesis of both cobalamin coenzymes was deficient in cultured skin fibroblasts. The cblF defect was confirmed by somatic complementation analysis. Sequencing of LMBRD1 revealed the novel deletion c.1405delG (p.D469fsX38) on both alleles. Real-time polymerase chain reaction (PCR) revealed reduced messenger RNA (mRNA) levels in patient fibroblasts compared with controls. Transfection of patient fibroblasts with the LMBD1 wild-type complement DNA (cDNA) rescued coenzyme synthesis and function, confirming this new deletion as an additional cause of the cblF defect. This case adds to the spectrum of clinical presentations and mutations of this rare disorder of lysosomal transport.
Faculties and Departments: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:Kluwer
ISSN:0141-8955
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Dec 2012 13:04
Deposited On:07 Dec 2012 13:03

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