Eur J Hum Genet.: auth.: A.Reymond , co-auth.: group Xenarios

Eur J Hum Genet. 2015 Oct 21. doi: 10.1038/ejhg.2015.227. [Epub ahead of print]

West syndrome caused by homozygous variant in the evolutionary conserved gene encoding the mitochondrial elongation factor GUF1.


West syndrome (WS), defined by the triad of infantile spasms, pathognomonic hypsarrhythmia and developmental regression, is a rare epileptic disease affecting about 1:3500 live births. To get better insights on the genetic of this pathology, we exome-sequenced the members of a consanguineous family affected with isolated WS. We identified a homozygous variant (c.1825G>T/p.(Ala609Ser)) in the GUF1 gene in the three affected siblings. GUF1 encodes a protein essential in conditions that counteract faithful protein synthesis: it is able to remobilize stuck ribosomes and transiently inhibit the elongation process to optimize protein synthesis. The variant identified in the WS family changes an alanine residue conserved in all eukaryotic organisms and positioned within the tRNA-binding moiety of this nuclear genome-encoded mitochondrial translational elongation factor. Yeast complementation assays show that the activity of GUF1A609S is modified in suboptimal environments. We suggest a new link between improper assembly of respiratory chain complexes and WS.European Journal of Human Genetics advance online publication, 21 October 2015; doi:10.1038/ejhg.2015.227.