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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: 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
Zeitschrift: Human Mutation
Jahr der Veröffentlichung: 2016
Band: 37
Heftnummer: 8
Seitenbereich: 755-64
ISSN: 1059-7794
eISSN: 1098-1004


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.



FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Popp, Bernt Dr. med.
Humangenetisches Institut


Einrichtungen weiterer Autorinnen und Autoren

Assistance Publique-Hôpitaux de Paris (AP-HP)
Centre hospitalier universitaire (CHU) de Dijon Bourgogne
Children’s National Health System
Chu De Nancy - Hôpitaux De Brabois
Erasmus University Rotterdam (EUR) / Erasmus Universiteit Rotterdam
Hôpitaux universitaires de Strasbourg (HUS) / University Hospital Strasbourg
Icahn School of Medicine at Mount Sinai
Kaiser Permanente
Massachusetts General Hospital
Nantes University Hospital / Centre hospitalier universitaire de Nantes (CHU)
Pitié-Salpêtrière University Hospital / Hôpital universitaire Pitié-Salpêtrière
Université Bourgogne Franche-Comté
University Medical Centre Utrecht (UMC Utrecht)
University of Bergen


Zitierweisen

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: 

Zuletzt aktualisiert 2018-10-10 um 02:24