Pathogenic variants of novel gene causative of developmental delay
Variants in different genes may cause developmental delay and various syndromes. Researchers from USA, Saudi Arabia and Norway recently uncovered pathogenic gene variants causing developmental delay and intellectual disabilities in a gene not previously linked to genetic disease.
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N-terminal acetylation is the most common type of protein modification in human cells. The NatB enzyme complex is responsible for acetylating about 20% of all human proteins. NatB is composed of two proteins, both essential for NatB activity: NAA20 and NAA25.
Collaborating with clinicians and geneticists from the USA and Saudi Arabia, Kirsten Brønstad, Henriette Aksnes and Nina Glomnes from the Arnesen lab at the Dept. of Biomedicine, UiB, identified the first patients with pathogenic NAA20 variants. The affected children displayed partially overlapping phenotypes including developmental delay, intellectual disability, microcephaly and in some cases cardiac anomalies. Two different pathogenic gene variants were identified in five individuals in two different families. In Bergen, the variants were studied biochemically at the protein level, and experiments uncovered that both variants had a reduced capacity to form NatB complexes and to acetylate NatB substrates.
The study provides the affected families with an explanation to disease mechanisms and causality, and makes it possible to carry out genetic screening in the future. Further, it was established that protein N-terminal acetylation is essential for human physiology, and points to underlying mechanisms causing disease.
The project was supported by The Research Council of Norway, Helse Vest, and the Norwegian Cancer Society.
