Infection-triggered familial or recurrent cases of acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore, RANBP2

Serenella Servidei, Derek E. Neilson, Mark D. Adams, Caitlin M.D. Orr, Deborah K. Schelling, Robert M. Eiben, Douglas S. Kerr, Jane Anderson, Alexander G. Bassuk, Ann M. Bye, Anne-Marie Childs, Antonia Clarke, Yanick J. Crow, Maja Di Rocco, Christian Dohna-Schwake, Gregor Dueckers, Artemis D. Gika, Dimitris Gionnis, Mark P. Gorman, Padraic J. Grattan-SmithAnnette Hackenberg, Alice Kuster, Markus G. Lentschig, Eduardo Lopez-Laso, Elysa J. Marco, Sotiria Mastroyianni, Julie Perrier, Thomas Schmitt-Mechelke, Angeliki Skardoutsou, Peter Uldall, Marjo S. Van Der Knaap, Karrie C. Goglin, David L. Tefft, Cristin Aubin, Philip De Jager, David Hafler, Matthew L. Warman

Risultato della ricerca: Contributo in rivistaArticolo in rivista

184 Citazioni (Scopus)

Abstract

Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). However, we identified a 7 Mb interval containing a susceptibility locus (ANE1) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait. We now report that all affected individuals and obligate carriers in this family are heterozygous for a missense mutation (c.1880C-->T, p.Thr585Met) in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2). To determine whether this mutation is the susceptibility allele, we screened controls and other patients with ANE who are unrelated to the index family. Patients from 9 of 15 additional kindreds with familial or recurrent ANE had the identical mutation. It arose de novo in two families and independently in several other families. Two other patients with familial ANE had different RANBP2 missense mutations that altered conserved residues. None of the three RANBP2 missense mutations were found in 19 patients with isolated ANE or in unaffected controls. We conclude that missense mutations in RANBP2 are susceptibility alleles for familial and recurrent cases of ANE.
Lingua originaleEnglish
pagine (da-a)44-51
Numero di pagine8
RivistaAmerican Journal of Human Genetics
Volume84
DOI
Stato di pubblicazionePubblicato - 2009

Keywords

  • Genetic Predisposition to Disease
  • Influenza, Human
  • Leukoencephalitis, Acute Hemorrhagic
  • Molecular Chaperones
  • Nuclear Pore Complex Proteins

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