First published on UiB.no June 13, 2019.
N-terminal acetylation is a very common protein modification and NAA10 is the major responsible enzyme in human cells. Here we found a novel pathological NAA10 variant, NAA10 p. (R83H), in two boys with developmental delay and intellectual disabilities.
In collaboration with clinicians at the Odense University Hospital in Denmark and Temple Street Children’s Hospital, Dublin, Ireland, master student Anni Sofie Geithus and researcher Rasmus Ree from the Arnesen lab found a novel pathological variant of NAA10. Two boys with overlapping phenotypes were independently examined in Denmark and Ireland, and by exome sequencing it was found that they both harbor a novel variant of the NAA10 gene. The NAA10 protein forms the NatA complex together with NAA15, and is responsible for acetylating thousands of proteins in human cells. The NAT-group at UiB was then contacted, and Geithus and Ree found that this special variant of NAA10 exhibited a very reduced catalytic activity. This is most likely caused by the fact that Arg83 is in direct contact with the first substrate of the reaction, Acetyl Coenzyme A, and a change to His83 may disrupt this interaction.
This study sheds light on the physiological impact of protein N-terminal acetylation in humans, since these two boys were found to have a number of fenotypes including developmental delay, intellectual disabilities, ADHD like behavior, epilepsy, and cardiac anomalies.
Rasmus Ree, Anni Sofie Geithus, Pernille Mathiesen Tørring, Kristina Pilekær Sørensen, Mads Damkjær, DDD study, Sally Ann Lynch, and Thomas Arnesen
BMC Med Genet. 2019 Jun 7;20(1):101.