Περίληψη:
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. © 2009 The American Society of Human Genetics.
Συγγραφείς:
Neilson, D.E.
Adams, M.D.
Orr, C.M.D.
Schelling, D.K.
Eiben, R.M.
Kerr, D.S.
Anderson, J.
Bassuk, A.G.
Bye, A.M.
Childs, A.-M.
Clarke, A.
Crow, Y.J.
Di Rocco, M.
Dohna-Schwake, C.
Dueckers, G.
Fasano, A.E.
Gika, A.D.
Gionnis, D.
Gorman, M.P.
Grattan-Smith, P.J.
Hackenberg, A.
Kuster, A.
Lentschig, M.G.
Lopez-Laso, E.
Marco, E.J.
Mastroyianni, S.
Perrier, J.
Schmitt-Mechelke, T.
Servidei, S.
Skardoutsou, A.
Uldall, P.
van der Knaap, M.S.
Goglin, K.C.
Tefft, D.L.
Aubin, C.
de Jager, P.
Hafler, D.
Warman, M.L.
Λέξεις-κλειδιά:
methionine; nucleoporin; ran binding protein 2; threonine; unclassified drug, acute necrotizing encephalopathy; allele; amino acid substitution; article; Asian; autosomal dominant inheritance; brain disease; Caucasian; controlled study; family study; gene locus; gene mutation; genetic screening; genetic susceptibility; heterozygosity; high performance liquid chromatography; human; human cell; influenza; major clinical study; missense mutation; Negro; penetrance; priority journal; race difference; reverse transcription polymerase chain reaction; RNA virus infection; sequence analysis, Exons; Genetic Predisposition to Disease; Humans; Influenza, Human; Leukoencephalitis, Acute Hemorrhagic; Molecular Chaperones; Mutation, Missense; Mycoplasma pneumoniae; Nuclear Pore Complex Proteins; Paramyxoviridae Infections; Pedigree; Pneumonia, Mycoplasma; Recurrence
