Abstract
N-Alpha-Acetylation is one of the most common co-Translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-Terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder. Additionally, some subjects present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. One of the individuals is an 11-year-old boy with a frameshift variant in exon 7 of NAA10, who presents most notably with microphthalmia, which confirms a prior finding with a single family with Lenz microphthalmia syndrome. Biochemical analyses of variants as part of the human NatA complex, as well as enzymatic analyses with and without the HYPK regulatory subunit, help to explain some of the phenotypic differences seen among the different variants.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2900-2919 |
| Number of pages | 20 |
| Journal | Human Molecular Genetics |
| Volume | 28 |
| Issue number | 17 |
| DOIs | |
| State | Published - Sep 1 2019 |
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All Science Journal Classification (ASJC) codes
- Molecular Biology
- Genetics
- Genetics(clinical)
Cite this
Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15. / Cheng, Hanyin; Gottlieb, Leah; Marchi, Elaine; Kleyner, Robert; Bhardwaj, Puja; Rope, Alan F.; Rosenheck, Sarah; Moutton, Sébastien; Philippe, Christophe; Eyaid, Wafaa; Alkuraya, Fowzan S.; Toribio, Janet; Mena, Rafael; Prada, Carlos E.; Stessman, Holly; Bernier, Raphael; Wermuth, Marieke; Kauffmann, Birgit; Blaumeiser, Bettina; Kooy, R. Frank; Baralle, Diana; Mancini, Grazia M.S.; Conway, Simon J.; Xia, Fan; Chen, Zhao; Meng, Linyan; Mihajlovic, Ljubisa; Marmorstein, Ronen; Lyon, Gholson J.
In: Human Molecular Genetics, Vol. 28, No. 17, 01.09.2019, p. 2900-2919.Research output: Contribution to journal › Article
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TY - JOUR
T1 - Phenotypic and biochemical analysis of an international cohort of individuals with variants in NAA10 and NAA15
AU - Cheng, Hanyin
AU - Gottlieb, Leah
AU - Marchi, Elaine
AU - Kleyner, Robert
AU - Bhardwaj, Puja
AU - Rope, Alan F.
AU - Rosenheck, Sarah
AU - Moutton, Sébastien
AU - Philippe, Christophe
AU - Eyaid, Wafaa
AU - Alkuraya, Fowzan S.
AU - Toribio, Janet
AU - Mena, Rafael
AU - Prada, Carlos E.
AU - Stessman, Holly
AU - Bernier, Raphael
AU - Wermuth, Marieke
AU - Kauffmann, Birgit
AU - Blaumeiser, Bettina
AU - Kooy, R. Frank
AU - Baralle, Diana
AU - Mancini, Grazia M.S.
AU - Conway, Simon J.
AU - Xia, Fan
AU - Chen, Zhao
AU - Meng, Linyan
AU - Mihajlovic, Ljubisa
AU - Marmorstein, Ronen
AU - Lyon, Gholson J.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - N-Alpha-Acetylation is one of the most common co-Translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-Terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder. Additionally, some subjects present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. One of the individuals is an 11-year-old boy with a frameshift variant in exon 7 of NAA10, who presents most notably with microphthalmia, which confirms a prior finding with a single family with Lenz microphthalmia syndrome. Biochemical analyses of variants as part of the human NatA complex, as well as enzymatic analyses with and without the HYPK regulatory subunit, help to explain some of the phenotypic differences seen among the different variants.
AB - N-Alpha-Acetylation is one of the most common co-Translational protein modifications in humans and is essential for normal cell function. NAA10 encodes for the enzyme NAA10, which is the catalytic subunit in the N-Terminal acetyltransferase A (NatA) complex. The auxiliary and regulatory subunits of the NatA complex are NAA15 and Huntington-interacting protein (HYPK), respectively. Through a genotype-first approach with exome sequencing, we identified and phenotypically characterized 30 individuals from 30 unrelated families with 17 different de novo or inherited, dominantly acting missense variants in NAA10 or NAA15. Clinical features of affected individuals include variable levels of intellectual disability, delayed speech and motor milestones and autism spectrum disorder. Additionally, some subjects present with mild craniofacial dysmorphology, congenital cardiac anomalies and seizures. One of the individuals is an 11-year-old boy with a frameshift variant in exon 7 of NAA10, who presents most notably with microphthalmia, which confirms a prior finding with a single family with Lenz microphthalmia syndrome. Biochemical analyses of variants as part of the human NatA complex, as well as enzymatic analyses with and without the HYPK regulatory subunit, help to explain some of the phenotypic differences seen among the different variants.
UR - http://www.scopus.com/inward/record.url?scp=85068020296&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068020296&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddz111
DO - 10.1093/hmg/ddz111
M3 - Article
C2 - 31127942
AN - SCOPUS:85068020296
VL - 28
SP - 2900
EP - 2919
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 17
ER -