- Simon, Mariella T;
- Ng, Bobby G;
- Friederich, Marisa W;
- Wang, Raymond Y;
- Boyer, Monica;
- Kircher, Martin;
- Collard, Renata;
- Buckingham, Kati J;
- Chang, Richard;
- Shendure, Jay;
- Nickerson, Deborah A;
- Bamshad, Michael J;
- Genomics, University of Washington Center for Mendelian;
- Van Hove, Johan LK;
- Freeze, Hudson H;
- Abdenur, Jose E
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.