Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital

Biochemical analysis of novel NAA10 variants suggests distinct pathogenic mechanisms involving impaired protein N-terminal acetylation

Research output: Contribution to journalJournal articlepeer-review

  1. Mutations in BCOR, a co-repressor of CRX/OTX2, are associated with early-onset retinal degeneration

    Research output: Contribution to journalJournal articlepeer-review

  2. Identification and analysis of deletion breakpoints in four Mohr-Tranebjærg syndrome (MTS) patients

    Research output: Contribution to journalJournal articlepeer-review

  3. Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder

    Research output: Contribution to journalJournal articlepeer-review

  4. High Resolution Analysis of DMPK Hypermethylation and Repeat Interruptions in Myotonic Dystrophy Type 1

    Research output: Contribution to journalJournal articlepeer-review

  5. Neurodevelopmental Disorders Associated with PSD-95 and Its Interaction Partners

    Research output: Contribution to journalReviewpeer-review

View graph of relations

NAA10 is the catalytic subunit of the N-terminal acetyltransferase complex, NatA, which is responsible for N-terminal acetylation of nearly half the human proteome. Since 2011, at least 21 different NAA10 missense variants have been reported as pathogenic in humans. The clinical features associated with this X-linked condition vary, but commonly described features include developmental delay, intellectual disability, cardiac anomalies, brain abnormalities, facial dysmorphism and/or visual impairment. Here, we present eight individuals from five families with five different de novo or inherited NAA10 variants. In order to determine their pathogenicity, we have performed biochemical characterisation of the four novel variants c.16G>C p.(A6P), c.235C>T p.(R79C), c.386A>C p.(Q129P) and c.469G>A p.(E157K). Additionally, we clinically describe one new case with a previously identified pathogenic variant, c.384T>G p.(F128L). Our study provides important insight into how different NAA10 missense variants impact distinct biochemical functions of NAA10 involving the ability of NAA10 to perform N-terminal acetylation. These investigations may partially explain the phenotypic variability in affected individuals and emphasise the complexity of the cellular pathways downstream of NAA10.

Original languageEnglish
JournalHuman Genetics
Issue number8
Pages (from-to)1355-1369
Number of pages15
Publication statusPublished - Aug 2022

Bibliographical note

© 2022. The Author(s).

    Research areas

  • Acetylation, Genes, X-Linked, Humans, Intellectual Disability/genetics, N-Terminal Acetyltransferase A/genetics, N-Terminal Acetyltransferase E/genetics

ID: 73251879