Journal article

Damaging de novo missense variants in EEF1A2 lead to a developmental and degenerative epileptic-dyskinetic encephalopathy

Gemma L Carvill, Katherine L Helbig, Candace T Myers, Marcello Scala, Robert Huether, Sara Lewis, Tyler N Kruer, Brandon S Guida, Somayeh Bakhtiari, Joy Sebe, Sha Tang, Heather Stickney, Sehribani Ulusoy Oktay, Ashwin A Bhandiwad, Keri Ramsey, Vinodh Narayanan, Timothy Feyma, Luis O Rohena, Andrea Accogli, Mariasavina Severino Show all

Human Mutation | WILEY | Published : 2020


Heterozygous de novo variants in the eukaryotic elongation factor EEF1A2 have previously been described in association with intellectual disability and epilepsy but never functionally validated. Here we report 14 new individuals with heterozygous EEF1A2 variants. We functionally validate multiple variants as protein-damaging using heterologous expression and complementation analysis. Our findings allow us to confirm multiple variants as pathogenic and broaden the phenotypic spectrum to include dystonia/choreoathetosis, and in some cases a degenerative course with cerebral and cerebellar atrophy. Pathogenic variants appear to act via a haploinsufficiency mechanism, disrupting both the protein..

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University of Melbourne Researchers