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

Journal of Inherited Metabolic Disease
Susann GailusFrank Rutsch

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. Transfecti...Continue Reading

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Citations

Feb 23, 2010·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Susann GailusFrank Rutsch
May 7, 2010·Journal of Inherited Metabolic Disease·Frank RutschBrian Fowler
Dec 1, 2010·Expert Reviews in Molecular Medicine·D Sean Froese, Roy A Gravel
May 23, 2014·Leukemia & Lymphoma·Nathalie Douet-GuilbertMarc De Braekeleer
Mar 13, 2015·Journal of Inherited Metabolic Disease·Martina HuemerHenk J Blom
Mar 13, 2014·Developmental Medicine and Child Neurology·Maja von der HagenAngela M Kaindl
Nov 24, 2016·Molecular Aspects of Medicine·Luciana Hannibal, Henk J Blom
Jun 3, 2017·The Journal of Biological Chemistry·Victoria FettelschossMatthias R Baumgartner
May 10, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Luciana HannibalDonald W Jacobsen
Dec 26, 2018·Journal of Medical Biochemistry·Khalid M Al-BataynehGreg Eaton
Feb 12, 2011·American Journal of Medical Genetics. Part C, Seminars in Medical Genetics·David Watkins, David S Rosenblatt

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