{Reference Type}: Case Reports
{Title}: Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency.
{Author}: Simon MT;Ng BG;Friederich MW;Wang RY;Boyer M;Kircher M;Collard R;Buckingham KJ;Chang R;Shendure J;Nickerson DA;Bamshad MJ; ;Van Hove JLK;Freeze HH;Abdenur JE;
{Journal}: Mitochondrion
{Volume}: 34
{Issue}: 0
{Year}: 05 2017
{Factor}: 4.534
{DOI}: 10.1016/j.mito.2017.02.004
{Abstract}: We report the clinical, biochemical, and molecular findings in two brothers with encephalopathy and multi-systemic disease. Abnormal transferrin glycoforms were suggestive of a type I congenital disorder of glycosylation (CDG). While exome sequencing was negative for CDG related candidate genes, the testing revealed compound heterozygous mutations in the mitochondrial elongation factor G gene (GFM1). One of the mutations had been reported previously while the second, novel variant was found deep in intron 6, activating a cryptic splice site. Functional studies demonstrated decreased GFM1 protein levels, suggested disrupted assembly of mitochondrial complexes III and V and decreased activities of mitochondrial complexes I and IV, all indicating combined OXPHOS deficiency.