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Mol Genet Metab. 2017 Dec;122(4):182-188. doi: 10.1016/j.ymgme.2017.10.014. Epub 2017 Nov 2.

An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency.

Author information

1
Research Unit for Molecular Medicine, Department of Clinical Medicine, Aarhus University and University Hospital, 8200 Aarhus N, Denmark.
2
Department of Biochemistry and Molecular Biology, The Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark.
3
Department of Medical Biochemistry, Oslo University Hospital, Oslo, Norway.
4
Ostfold Hospital Trust, Women's and Children's Department, Norway.
5
Department of Pediatrics, Oslo University Hospital, Oslo, Norway.
6
Department of Biochemistry and Molecular Biology, The Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, Denmark. Electronic address: bragea@bmb.sdu.dk.

Abstract

Vitamin B2, riboflavin is essential for cellular function, as it participates in a diversity of redox reactions central to human metabolism, through its role as precursor for the cofactors flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are electron carriers. The electron transfer flavoprotein (ETF) and its dehydrogenase (ETFDH), uses FAD as cofactor. The ETF and ETFDH are forming the electron transport pathway for many mitochondrial flavoprotein dehydrogenases involved in fatty acid, amino acid and choline metabolism. A variation in either ETF or ETFDH causes multiple acyl-CoA dehydrogenation deficiency (MADD), but genetic variations in the riboflavin metabolism or transportation of riboflavin can also cause MADD. The most common variations are located in the riboflavin transporter 2 (RFVT2) and 3 (RFVT3), that are highly expressed in brain and intestinal tissues, respectively. Deficiency of riboflavin transporter 1 (RFVT1), encoded by the SLC52A1 gene, highly expressed in the placenta, has only been reported once. We here report a case of transient MADD, caused by a heterozygous intronic variation, c.1134+11G>A, in the SLC52A1 gene encoding RFVT1. This variation creates a binding site for the splice inhibitory hnRNP A1 protein and causes exon 4 skipping. Riboflavin deficiency and maternal malnutrition during pregnancy might have been the determining factor in the outcome of this case.

KEYWORDS:

MADD; Riboflavin; Splicing silencer; hnRNP A1

PMID:
29122468
DOI:
10.1016/j.ymgme.2017.10.014
[Indexed for MEDLINE]

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