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

Signe Mosegaard, Gitte Hoffmann Bruun, Karen Freund Flyvbjerg, Yngve Thomas Bliksrud, Niels Gregersen, Maja Dembic, Ellen Annexstad, Trine Tangeraas, Rikke Katrine Jentoft Olsen, Brage S Andresen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftMolecular Genetics and Metabolism
Vol/bind122
Udgave nummer4
Sider (fra-til)182-188
ISSN1096-7192
DOI
StatusUdgivet - 2017

Fingeraftryk

Acyl Coenzyme A
Riboflavin
Dehydrogenation
Exons
Electron-Transferring Flavoproteins
Riboflavin Deficiency
Flavin-Adenine Dinucleotide
Metabolism
Oxidoreductases
Flavin Mononucleotide
Flavoproteins
Electron Transport
Choline
Malnutrition
Placenta
Gene encoding
Redox reactions
Fatty Acids
Mothers
Electrons

Citer dette

Mosegaard, Signe ; Bruun, Gitte Hoffmann ; Flyvbjerg, Karen Freund ; Bliksrud, Yngve Thomas ; Gregersen, Niels ; Dembic, Maja ; Annexstad, Ellen ; Tangeraas, Trine ; Olsen, Rikke Katrine Jentoft ; Andresen, Brage S. / An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. I: Molecular Genetics and Metabolism. 2017 ; Bind 122, Nr. 4. s. 182-188.
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title = "An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency",
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.",
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An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. / Mosegaard, Signe; Bruun, Gitte Hoffmann; Flyvbjerg, Karen Freund; Bliksrud, Yngve Thomas; Gregersen, Niels; Dembic, Maja; Annexstad, Ellen; Tangeraas, Trine; Olsen, Rikke Katrine Jentoft; Andresen, Brage S.

I: Molecular Genetics and Metabolism, Bind 122, Nr. 4, 2017, s. 182-188.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - An intronic variation in SLC52A1 causes exon skipping and transient riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency

AU - Mosegaard, Signe

AU - Bruun, Gitte Hoffmann

AU - Flyvbjerg, Karen Freund

AU - Bliksrud, Yngve Thomas

AU - Gregersen, Niels

AU - Dembic, Maja

AU - Annexstad, Ellen

AU - Tangeraas, Trine

AU - Olsen, Rikke Katrine Jentoft

AU - Andresen, Brage S

N1 - Copyright © 2017. Published by Elsevier Inc.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1016/j.ymgme.2017.10.014

DO - 10.1016/j.ymgme.2017.10.014

M3 - Journal article

VL - 122

SP - 182

EP - 188

JO - Molecular Genetics and Metabolism

JF - Molecular Genetics and Metabolism

SN - 1096-7192

IS - 4

ER -