A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient
JournalArticle (Originalarbeit in einer wissenschaftlichen Zeitschrift)
ID 1194081
Author(s) Gailus, Susann; Suormala, Terttu; Malerczyk-Aktas, Ayse Gül; Toliat, Mohammad R; Wittkampf, Tanja; Stucki, Martin; Nürnberg, Peter; Fowler, Brian; Hennermann, Julia B; Rutsch, Frank
Author(s) at UniBasel Fowler, Brian
Year 2010
Title A novel mutation in LMBRD1 causes the cblF defect of vitamin B(12) metabolism in a Turkish patient
Journal Journal of Inherited Metabolic Disease
Volume 33
Number 1
Pages / Article-Number 17-24
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.
Publisher Kluwer
ISSN/ISBN 0141-8955
edoc-URL http://edoc.unibas.ch/dok/A6004311
Full Text on edoc No
Digital Object Identifier DOI 10.1007/s10545-009-9032-7
PubMed ID http://www.ncbi.nlm.nih.gov/pubmed/20127417
ISI-Number WOS:000274949100003
Document type (ISI) Journal Article

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