Activation of a cryptic splice site in the mitochondrial elongation factor GFM1 causes combined OXPHOS deficiency

作者：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; Van Hove Johan L K; Freeze Hudson H; Abdenur Jose E

来源：Mitochondrion, 2017, 34: 84-90.

DOI：10.1016/j.mito.2017.02.004

• GFM1
• Mitochondrial disease
• Congenital disorders of glycosylation
• Mitochondrial elongation factor
• Cryptic splice site

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.

• 出版日期2017-5