Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency

Chloé Saunier, Svein Isungset Støve, Bernt Popp, Bénédicte Gérard, Marina Blenski, Nicholas AhMew, Charlotte de Bie, Paula Goldenberg, Bertrand Isidor, Boris Keren, Bruno Leheup, Laetitia Lampert, Cyril Mignot, Kamer Tezcan, Grazia M S Mancini, Caroline Nava, Melissa P. Wasserstein, Ange Line Bruel, Julien Thevenon, Alice Masurel & 11 others Yannis Duffourd, Paul Kuentz, Frédéric Huet, Jean Baptiste Rivière, Marjon van Slegtenhorst, Laurence Faivre, Amélie Piton, André Reis, Thomas Arnesen, Christel Thauvin-Robinet, Christiane Zweier

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

N-terminal acetylation is a common protein modification in eukaryotes associated with numerous cellular processes. Inherited mutations in NAA10, encoding the catalytic subunit of the major N-terminal acetylation complex NatA have been associated with diverse, syndromic X-linked recessive disorders, whereas de novo missense mutations have been reported in one male and one female individual with severe intellectual disability but otherwise unspecific phenotypes. Thus, the full genetic and clinical spectrum of NAA10 deficiency is yet to be delineated. We identified three different novel and one known missense mutation in NAA10, de novo in 11 females, and due to maternal germ line mosaicism in another girl and her more severely affected and deceased brother. In vitro enzymatic assays for the novel, recurrent mutations p.(Arg83Cys) and p.(Phe128Leu) revealed reduced catalytic activity. X-inactivation was random in five females. The core phenotype of X-linked NAA10-related N-terminal-acetyltransferase deficiency in both males and females includes developmental delay, severe intellectual disability, postnatal growth failure with severe microcephaly, and skeletal or cardiac anomalies. Genotype–phenotype correlations within and between both genders are complex and may include various factors such as location and nature of mutations, enzymatic stability and activity, and X-inactivation in females.

Original languageEnglish (US)
Pages (from-to)755-764
Number of pages10
JournalHuman Mutation
Volume37
Issue number8
DOIs
StatePublished - Aug 1 2016
Externally publishedYes

Fingerprint

Acetylation
Phenotype
X Chromosome Inactivation
Missense Mutation
Intellectual Disability
Mutation
N-Terminal Acetyltransferases
Microcephaly
Mosaicism
Enzyme Assays
Eukaryota
Germ Cells
Siblings
Catalytic Domain
Mothers
Growth
Proteins

Keywords

  • intellectual disability
  • N-terminal acetylation
  • NAA10
  • X-linked

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Saunier, C., Støve, S. I., Popp, B., Gérard, B., Blenski, M., AhMew, N., ... Zweier, C. (2016). Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency. Human Mutation, 37(8), 755-764. https://doi.org/10.1002/humu.23001

Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency. / Saunier, Chloé; Støve, Svein Isungset; Popp, Bernt; Gérard, Bénédicte; Blenski, Marina; AhMew, Nicholas; de Bie, Charlotte; Goldenberg, Paula; Isidor, Bertrand; Keren, Boris; Leheup, Bruno; Lampert, Laetitia; Mignot, Cyril; Tezcan, Kamer; Mancini, Grazia M S; Nava, Caroline; Wasserstein, Melissa P.; Bruel, Ange Line; Thevenon, Julien; Masurel, Alice; Duffourd, Yannis; Kuentz, Paul; Huet, Frédéric; Rivière, Jean Baptiste; van Slegtenhorst, Marjon; Faivre, Laurence; Piton, Amélie; Reis, André; Arnesen, Thomas; Thauvin-Robinet, Christel; Zweier, Christiane.

In: Human Mutation, Vol. 37, No. 8, 01.08.2016, p. 755-764.

Research output: Contribution to journalArticle

Saunier, C, Støve, SI, Popp, B, Gérard, B, Blenski, M, AhMew, N, de Bie, C, Goldenberg, P, Isidor, B, Keren, B, Leheup, B, Lampert, L, Mignot, C, Tezcan, K, Mancini, GMS, Nava, C, Wasserstein, MP, Bruel, AL, Thevenon, J, Masurel, A, Duffourd, Y, Kuentz, P, Huet, F, Rivière, JB, van Slegtenhorst, M, Faivre, L, Piton, A, Reis, A, Arnesen, T, Thauvin-Robinet, C & Zweier, C 2016, 'Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency', Human Mutation, vol. 37, no. 8, pp. 755-764. https://doi.org/10.1002/humu.23001
Saunier C, Støve SI, Popp B, Gérard B, Blenski M, AhMew N et al. Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency. Human Mutation. 2016 Aug 1;37(8):755-764. https://doi.org/10.1002/humu.23001
Saunier, Chloé ; Støve, Svein Isungset ; Popp, Bernt ; Gérard, Bénédicte ; Blenski, Marina ; AhMew, Nicholas ; de Bie, Charlotte ; Goldenberg, Paula ; Isidor, Bertrand ; Keren, Boris ; Leheup, Bruno ; Lampert, Laetitia ; Mignot, Cyril ; Tezcan, Kamer ; Mancini, Grazia M S ; Nava, Caroline ; Wasserstein, Melissa P. ; Bruel, Ange Line ; Thevenon, Julien ; Masurel, Alice ; Duffourd, Yannis ; Kuentz, Paul ; Huet, Frédéric ; Rivière, Jean Baptiste ; van Slegtenhorst, Marjon ; Faivre, Laurence ; Piton, Amélie ; Reis, André ; Arnesen, Thomas ; Thauvin-Robinet, Christel ; Zweier, Christiane. / Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency. In: Human Mutation. 2016 ; Vol. 37, No. 8. pp. 755-764.
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