NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy

Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.publishedVersio

NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy

Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants

Ophthalmic genetics in South America Malena

South America comprises of heterogeneous topographies, populations, and health care systems. Therefore, it is not surprising to see differences among the countries regarding expertise, education, and practices of ophthalmic genetics for patients with rare eye diseases. Nevertheless, common challenges such as limited genetics training in medical schools and among ophthalmologists, scarcity of diagnostic tools for phenotyping, and expensive genetic testing not covered by the public healthcare systems, are seen in all of them. Here, we provide a detailed report of the current status of ophthalmic genetics, described by the personal views of local ophthalmologists from Brazil, Colombia, Argentina, and Chile. By reporting our strengths and weaknesses as a region, we intend to highlight the need for guidelines on how to manage these patients aligned with public health policies. Our region contributes to research worldwide, with thousands of well diagnosed patients from a number of unique and genetically diverse populations. The constant expansion of ophthalmic genetics and molecular diagnostics requires us to join forces to collaborate across South America and with other countries to improve access to next-generation diagnostics and ultimately improve patient care.NEI Intramural Fund