Format

Send to

Choose Destination
Mitochondrion. 2017 May;34:84-90. doi: 10.1016/j.mito.2017.02.004. Epub 2017 Feb 12.

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

Author information

1
Division of Metabolic Disorders, CHOC Children's, Orange, CA, USA; Department of Developmental and Cell Biology, University of California Irvine, Irvine, CA, USA.
2
Human Genetics Program, Sanford Children's Health Research Center, Sanford-Burnham-Prebys Medical Discovery Institute, La Jolla, CA, USA.
3
Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado, Aurora, CO, USA.
4
Division of Metabolic Disorders, CHOC Children's, Orange, CA, USA; Department of Pediatrics, University of California Irvine, Irvine, CA, USA.
5
Division of Metabolic Disorders, CHOC Children's, Orange, CA, USA.
6
Department of Genome Sciences, University of Washington, Seattle, WA, USA.
7
Department of Pediatrics, University of Washington, Seattle, WA, USA.
8
Department of Genome Sciences, University of Washington, Seattle, WA, USA; Howard Hughes Medical Institute, University of Washington, Seattle, WA, USA.
9
Department of Genome Sciences, University of Washington, Seattle, WA, USA; Department of Pediatrics, University of Washington, Seattle, WA, USA.
10
Division of Metabolic Disorders, CHOC Children's, Orange, CA, USA; Department of Pediatrics, University of California Irvine, Irvine, CA, USA. Electronic address: jabdenur@choc.org.

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.

KEYWORDS:

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

PMID:
28216230
PMCID:
PMC5444868
DOI:
10.1016/j.mito.2017.02.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center