Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness

Détails

ID Serval
serval:BIB_08985CDE10C0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Human adenylate kinase 2 deficiency causes a profound hematopoietic defect associated with sensorineural deafness
Périodique
Nat Genet
Auteur(s)
Lagresle-Peyrou C., Six E. M., Picard C., Rieux-Laucat F., Michel V., Ditadi A., Demerens-de Chappedelaine C., Morillon E., Valensi F., Simon-Stoos K. L., Mullikin J. C., Noroski L. M., Besse C., Wulffraat N. M., Ferster A., Abecasis M. M., Calvo F., Petit C., Candotti F., Abel L., Fischer A., Cavazzana-Calvo M.
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
01/2009
Volume
41
Numéro
1
Pages
106-11
Langue
anglais
Notes
Lagresle-Peyrou, Chantal
Six, Emmanuelle M
Picard, Capucine
Rieux-Laucat, Frederic
Michel, Vincent
Ditadi, Andrea
Demerens-de Chappedelaine, Corinne
Morillon, Estelle
Valensi, Francoise
Simon-Stoos, Karen L
Mullikin, James C
Noroski, Lenora M
Besse, Celine
Wulffraat, Nicolas M
Ferster, Alina
Abecasis, Manuel M
Calvo, Fabien
Petit, Christine
Candotti, Fabio
Abel, Laurent
Fischer, Alain
Cavazzana-Calvo, Marina
eng
Z01 HG000122-10/Intramural NIH HHS/
Z99 HG999999/Intramural NIH HHS/
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Nat Genet. 2009 Jan;41(1):106-11. doi: 10.1038/ng.278. Epub 2008 Nov 30.
Résumé
Reticular dysgenesis is an autosomal recessive form of human severe combined immunodeficiency characterized by an early differentiation arrest in the myeloid lineage and impaired lymphoid maturation. In addition, affected newborns have bilateral sensorineural deafness. Here we identify biallelic mutations in AK2 (adenylate kinase 2) in seven individuals affected with reticular dysgenesis. These mutations result in absent or strongly decreased protein expression. We then demonstrate that restoration of AK2 expression in the bone marrow cells of individuals with reticular dysgenesis overcomes the neutrophil differentiation arrest, underlining its specific requirement in the development of a restricted set of hematopoietic lineages. Last, we establish that AK2 is specifically expressed in the stria vascularis region of the inner ear, which provides an explanation of the sensorineural deafness in these individuals. These results identify a previously unknown mechanism involved in regulation of hematopoietic cell differentiation and in one of the most severe human immunodeficiency syndromes.
Mots-clé
Adenylate Kinase/*deficiency/genetics/metabolism, Animals, Cell Differentiation, Cell Line, Ear, Inner/enzymology/pathology, Female, Gene Expression Regulation, Enzymologic, Hearing Loss, Sensorineural/*complications/*enzymology/genetics, Hematopoietic System/*pathology, Humans, Infant, Newborn, Isoenzymes/*deficiency/genetics/metabolism, Male, Mice, Mutation/genetics, Neutrophils/pathology, Pedigree, Protein Transport, Severe Combined Immunodeficiency/complications/enzymology/genetics/immunology
Pubmed
Création de la notice
01/11/2017 11:29
Dernière modification de la notice
03/03/2018 13:30
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