%0 Case Reports
%T Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency.
%A Simon MT
%A Ng BG
%A Friederich MW
%A Wang RY
%A Boyer M
%A Kircher M
%A Collard R
%A Buckingham KJ
%A Chang R
%A Shendure J
%A Nickerson DA
%A Bamshad MJ
%A  
%A Van Hove JLK
%A Freeze HH
%A Abdenur JE
%J Mitochondrion
%V 34
%N 0
%D 05 2017
%M 28216230
%F 4.534
%R 10.1016/j.mito.2017.02.004
%X 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.