Toward genotype phenotype correlations in GFM1 mutations

Louise Galmiche, Valérie Serre, Marine Beinat, Raïssa Zossou, Zahra Assouline, Anne Sophie Lebre, Florence Chretien, Ruthie Shenhav, Avraham Zeharia, Ann Saada, Vanessa Vedrenne, Nathalie Boddaert, Pascale de Lonlay, Marlène Rio, Arnold Munnich, Agnès Rötig*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Multiple respiratory chain deficiencies represent a common cause of mitochondrial diseases. We report two novel GFM1 mutations in two unrelated patients with encephalopathy and liver failure respectively. The first patient had intrauterine growth retardation, seizures, encephalopathy and developmental delay. Brain MRI showed hypoplasia of the vermis and severe pontine atrophy of the brainstem that were similar to those reported in patients with mitochondrial translation deficiencies. The second patient had liver failure with hypoglycemia. Respiratory chain analysis showed a complex IV deficiency in muscle of both patients. A 10K SNP genotyping detected several regions of homozygosity in the two patients. In vitro translation deficiency prompted us to study genes involved in mitochondrial translation. Therefore, we sequenced the GFM1 gene, encoding the mitochondrial translation factor EFG1, included in a shared homozygous region and identified two different homozygous mutations (R671C and L398P). Modeling studies of EFG1 protein suggested that the R671C mutation disrupts an inter-subunit interface and could locally destabilize the mutant protein. The second mutation (L398P) disrupted the H-bond network in a rich-beta-sheet domain, and may have a dramatic effect on local structure. GFM1 mutations have been seldom reported and are associated with different clinical presentation. By modeling the structure of the protein and the position of the various mutations we suggest that the clinical phenotypes of the patients could be related to the localization of the mutations.

Original languageEnglish
Pages (from-to)242-247
Number of pages6
Issue number2
StatePublished - Mar 2012


  • Encephalopathy
  • GFM1 translation elongation factor
  • Hepatic failure
  • Mitochondrial translation


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