Open AccessNovel de novo EEF 1A2 missense mutations causing epilepsy and intellectual disability
Author(s) -
Lam Wayne W.K.,
Millichap John J.,
Soares Dinesh C.,
Chin Richard,
McLellan Ailsa,
FitzPatrick David R.,
Elmslie Frances,
Lees Melissa M.,
Schaefer G. Bradley,
Abbott Catherine M.
Publication year - 2016
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.219
Subject(s) - missense mutation , intellectual disability , epilepsy , exome sequencing , gene , genetics , phenotype , mutation , biology , bioinformatics , medicine , neuroscience
Background Exome sequencing has led to the discovery of mutations in novel causative genes for epilepsy. One such gene is EEF 1A2 , encoding a neuromuscular specific translation elongation factor, which has been found to be mutated de novo in five cases of severe epilepsy. We now report on a further seven cases, each with a different mutation, of which five are newly described. Methods New cases were identified and sequenced through the Deciphering Developmental Disabilities project, via direct contact with neurologists or geneticists, or recruited via our website. Results All the mutations cause epilepsy and intellectual disability, but with a much wider range of severity than previously identified. All new cases share specific subtle facial dysmorphic features. Each mutation occurs at an evolutionarily highly conserved amino acid position indicating strong structural or functional selective pressure. Conclusions EEF 1A2 should be considered as a causative gene not only in cases of epileptic encephalopathy but also in children with less severe epilepsy and intellectual disability. The emergence of a possible discernible phenotype, a broad nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth may help in identifying patients with mutations in EEF 1A2 .