New NAA10 mutations identified in 11 girls and boys with development delays.

In recent years, several sporadic cases of NAA10 mutations have been identified in patients with varying degrees of developmental delays. NAA10 codes for an N-terminal acetyltransferase which acetylates the N-termini of approximately 40% of all globular proteins in humans. The first patients with NAA10 mutation causing N-terminal acetyltransferase deficiency was discovered in 2011. 8 boys from three generations in two unrelated families were suffering from a syndrome (later to be called Ogden syndrome) causing severe global development delays. All boys affected by Ogden syndrome died before becoming 2 years old. Since the initial discovery of Ogden syndrome, several patients with development delays and NAA10 mutations have been identified. In 2014, a frameshift mutation in NAA10 was identified as the cause of Lenz-Micropthalmia syndrome in 3 adult brothers. In 2015 two additional NAA10 mutations was identified in a 6 year old boy and a 3 year old girl with milder development delays, and later the same year a fifth NAA10 mutation was identified in two brothers with development delays.

In the curremt issue of Human Mutation, Svein Isungset Støve, Marina Blenski and Thomas Arnesen from the NAT-group at the Department of Molecular Biology in collaboration with geneticists from Germany, France, the Netherlands and the United States discovered and characterized 3 additional NAA10 mutations in a total of 11 patients with varying degrees of development delays. The discovery of these 11 new patients could indicate that NAA10 mutations as a cause of development delays are much more common than what was first anticipated. Interestingly, 10 out of the 11 patients identified and described in this article are girls, which is in great contrast to previously reported cases of NAA10 mutations which almost exclusively have been found in boys or grown up men. The new findings published in this issue of Human Mutation thus greatly increase the phenotypic spectrum associated with NAA10 mutations, and suggest that that genotype-phenotype correlations for these disorders are much more complex than first anticipated.