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

Saunier C, Stove SI, Popp B, Gerard 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 M, Bruel AL, Thevenon J, Masurel A, Duffourd Y, Kuentz P, Huet F, Riviere JB, Van Slegtenhorst M, Faivre L, Piton A, Reis A, Arnesen T, Thauvin-Robinet C, Zweier C (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Human Mutation Wiley-Blackwell

Book Volume: 37

Pages Range: 755-64

Journal Issue: 8

DOI: 10.1002/humu.23001

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.

Authors with CRIS profile

Bernt Popp Institute of Human Genetics André Wiesmann da Silva Reis Lehrstuhl für Humangenetik Christiane Zweier Lehrstuhl für Humangenetik

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Involved external institutions

Massachusetts General Hospital US United States (USA) (US) Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU) FR France (FR) Assistance Publique-Hôpitaux de Paris (AP-HP) FR France (FR) Centre Hospitalier Universitaire de Nancy / CHU Hôpitaux de Brabois FR France (FR) Pitié-Salpêtrière University Hospital / Hôpital universitaire Pitié-Salpêtrière FR France (FR) Kaiser Permanente US United States (USA) (US) Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam NL Netherlands (NL) Icahn School of Medicine at Mount Sinai US United States (USA) (US) Université Bourgogne Franche-Comté FR France (FR) Centre hospitalier universitaire (CHU) de Dijon Bourgogne FR France (FR) Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg FR France (FR) University of Bergen / Universitetet i Bergen NO Norway (NO) Children’s National Health System US United States (USA) (US) University Medical Centre Utrecht (UMC Utrecht) NL Netherlands (NL)

How to cite

APA:

Saunier, C., Stove, S.I., Popp, B., Gerard, B., Blenski, M., Ahmew, N.,... Zweier, C. (2016). Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency. Human Mutation, 37(8), 755-64. https://dx.doi.org/10.1002/humu.23001

MLA:

Saunier, Chloe, et al. "Expanding the Phenotype Associated with NAA10-Related N-Terminal Acetylation Deficiency." Human Mutation 37.8 (2016): 755-64.

BibTeX: Download