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dc.contributor.authorCasey, Jillian P.
dc.contributor.authorStøve, Svein Isungset
dc.contributor.authorMcGorrian, Catherine
dc.contributor.authorGalvin, Joseph
dc.contributor.authorBlenski, Marina
dc.contributor.authorDunne, Aimee
dc.contributor.authorEnnis, Sean
dc.contributor.authorBrett, Francesca
dc.contributor.authorKing, Mary D.
dc.contributor.authorArnesen, Thomas
dc.contributor.authorLynch, Sally Ann
dc.PublishedScientific Reports 2015, 5:16022eng
dc.description.abstractWe report two brothers from a non-consanguineous Irish family presenting with a novel syndrome characterised by intellectual disability, facial dysmorphism, scoliosis and long QT. Their mother has a milder phenotype including long QT. X-linked inheritance was suspected. Whole exome sequencing identified a novel missense variant (c.128 A > C; p.Tyr43Ser) in NAA10 (X chromosome) as the cause of the family’s disorder. Sanger sequencing confirmed that the mutation arose de novo in the carrier mother. NAA10 encodes the catalytic subunit of the major human N-terminal acetylation complex NatA. In vitro assays for the p.Tyr43Ser mutant enzyme showed a significant decrease in catalytic activity and reduced stability compared to wild-type Naa10 protein. NAA10 has previously been associated with Ogden syndrome, Lenz microphthalmia syndrome and non-syndromic developmental delay. Our findings expand the clinical spectrum of NAA10 and suggest that the proposed correlation between mutant Naa10 enzyme activity and phenotype severity is more complex than anticipated; the p.Tyr43Ser mutant enzyme has less catalytic activity than the p.Ser37Pro mutant associated with lethal Ogden syndrome but results in a milder phenotype. Importantly, we highlight the need for cardiac assessment in males and females with NAA10 variants as both patients and carriers can have long QT.en_US
dc.publisherNature Publishing Groupen_US
dc.rightsAttribution CC BYeng
dc.titleNAA10 mutation causing a novel intellectual disability syndrome with Long QT due to N-terminal acetyltransferase impairmenten_US
dc.typePeer reviewed
dc.typeJournal article

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