TY - JOUR
T1 - Novel SLC25A32 mutation in a patient with a severe neuromuscular phenotype
AU - Hellebrekers, Debby Mei
AU - Sallevelt, Suzanne C. E. H.
AU - Theunissen, Tom E. J.
AU - Hendrickx, Alexandra T. M.
AU - Gottschalk, Ralph W.
AU - Hoeijmakers, Janneke G. J.
AU - Habets, Daphna D.
AU - Bierau, Jorgen
AU - Schoonderwoerd, Kees G.
AU - Smeets, Hubert J. M.
PY - 2017/6
Y1 - 2017/6
N2 - 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.
AB - 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.
KW - MITOCHONDRIAL
KW - IDENTIFICATION
KW - TRANSPORTER
KW - RIBOFLAVIN
U2 - 10.1038/ejhg.2017.62
DO - 10.1038/ejhg.2017.62
M3 - Article
C2 - 28443623
SN - 1018-4813
VL - 25
SP - 886
EP - 888
JO - European Journal of Human Genetics
JF - European Journal of Human Genetics
IS - 7
ER -