A novel pathological variant of the acetyltransferase NAA10 causes disabilities
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.
Main content
In collaboration with clinicians at the Odense University Hospital in Denmark and听Temple Street Children鈥檚 Hospital, Dublin, Ireland,听master student Anni Sofie Geithus and researcher听Rasmus Ree from the听Arnesen lab found a novel听pathological variant听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听NatA complex together听with NAA15, and is responsible for acetylating thousands of proteins in human cells.听The NAT-group at听幸运飞艇计划 was then contacted, and听Geithus and听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听His83听may disrupt this interaction.
This study sheds light on the physiological impact of听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.
The study was recently published and can be read .听听
听