Abstract
In a 51-year-old patient of consanguineous parents with a severe neuromuscular phenotype of early-onset ataxia, myoclonia, dysarthria, muscle weakness and exercise intolerance, exome sequencing revealed a novel homozygous variant (c.-264_31delinsCTCACAAATGCTCA) in the mitochondrial FAD-transporter gene SLC25A32. Flavin adenine dinucleotide (FAD) is an essential co-factor for many mitochondrial enzymes and impaired mitochondrial FAD-transport was supported by a reduced oxidative phosphorylation complex II activity in the patient’s muscle, decreased ATP production in fibroblasts, and a deficiency of mitochondrial FAD-dependent enzymes. Clinically, the patient showed improvement upon riboflavin treatment, which is a precursor of FAD. Our results confirm the recently reported case of SLC25A32 as a cause of riboflavin-responsive disease. Our patient showed a more severe clinical phenotype compared with the reported patient, corresponding with the (most likely) complete absence of the SLC25A32-encoding MFT (Mitochondrial Folate Transporter) protein.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Schiff M, Veauville-Merllié A, Su CH et al: SLC25A32 mutations and riboflavin-responsive exercise intolerance. N Engl J Med 2016; 374: 795–797.
Sgobbo P, Pacelli C, Grattagliano I, Villani G, Cocco T : Carvedilol inhibits mitochondrial complex I and induces resistance to H2O2 -mediated oxidative insult in H9C2 myocardial cells. Biochim Biophys Acta 2007; 1767: 222–232.
Lek M, Karczewski KJ, Minikel EV et al: Analysis of protein-coding genetic variation in 60706 humans. Nature 2016; 536: 285–291.
Kozak M : Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell 1986; 44: 283–292.
Palmieri F : The mitochondrial transporter family SLC25: identification, properties and physiopathology. Mol Aspects Med 2013; 34: 465–484.
Spaan AN, Ijlst L, van Roermund CW et al: Identification of the human mitochondrial FAD transporter and its potential role in multiple acyl-CoA dehydrogenase deficiency. Mol Genet Metab 2005; 86: 441–447.
Henriques BJ, Lucas TG, Gomes CM et al: Therapeutic approaches using riboflavin in mitochondrial energy metabolism disorders. Curr Drug Targets 2016; 17: 1527–1534.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Additional information
Supplementary Information accompanies this paper on European Journal of Human Genetics website
Supplementary information
Rights and permissions
About this article
Cite this article
Hellebrekers, D., Sallevelt, S., Theunissen, T. et al. Novel SLC25A32 mutation in a patient with a severe neuromuscular phenotype. Eur J Hum Genet 25, 886–888 (2017). https://doi.org/10.1038/ejhg.2017.62
Received:
Revised:
Accepted:
Published:
Issue date:
DOI: https://doi.org/10.1038/ejhg.2017.62
This article is cited by
-
Upregulation of SLC25A32 in Tumorous Tissues of Patients with Non-Metastatic Colorectal Cancer: A Pilot Study
Indian Journal of Clinical Biochemistry (2025)
-
New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases
Nutrition & Metabolism (2023)
-
Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS
Nature Communications (2022)
-
Hypoketotic hypoglycemia without neuromuscular complications in patients with SLC25A32 deficiency
European Journal of Human Genetics (2022)
-
Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism
Cellular and Molecular Life Sciences (2022)
