title: EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement.
abstract: Pontocerebellar hypoplasia (PCH) type 1 is characterized by the co-occurrence of spinal anterior horn involvement and hypoplasia of the cerebellum and pons. EXOSC3 has been recently defined as a major cause of PCH type 1. Three different phenotypes showing variable severity have been reported. We identified a homozygous mutation [c.395A > C/p.D132A] in EXOSC3 in four patients with muscle hypotonia, developmental delay, spinal anterior horn involvement, and prolonged survival, consistent with the "mild PCH1 phenotype". Interestingly, isolated cerebellar hypoplasia limited to the hemispheres or involving both hemispheres and vermis was the main neuroradiologic finding, whereas the pontine volume was in the normal range for age. These findings strongly suggest that analysis of the EXOSC3 gene should be recommended also in patients with spinal anterior horn involvement and isolated cerebellar hypoplasia.
authors.affiliation: Neuroscience Department, Istituto G. Gaslini, Largo G. Gaslini 5, 16147 Genoa, Italy. roberta@biancheri.com
authors.forename: Roberta
authors.initials: R
authors.lastname: Biancheri
authors.forename: Denise
authors.initials: D
authors.lastname: Cassandrini
authors.forename: Francesca
authors.initials: F
authors.lastname: Pinto
authors.forename: Rosanna
authors.initials: R
authors.lastname: Trovato
authors.forename: Maja
authors.initials: M
authors.lastname: Di Rocco
authors.forename: Marisol
authors.initials: M
authors.lastname: Mirabelli-Badenier
authors.forename: Marina
authors.initials: M
authors.lastname: Pedemonte
authors.forename: Chiara
authors.initials: C
authors.lastname: Panicucci
authors.forename: Holger
authors.initials: H
authors.lastname: Trucks
authors.forename: Thomas
authors.initials: T
authors.lastname: Sander
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Andrea
authors.initials: A
authors.lastname: Rossi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Carlo
authors.initials: C
authors.lastname: Minetti
authors.forename: Filippo Maria
authors.initials: FM
authors.lastname: Santorelli
mesh_terms: D000293:Adolescent; D001933:Brain Stem / Q000473:pathology*; D002531:Cerebellum / Q000002:abnormalities* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000235:genetics / Q000473:pathology; D063326:Exosome Multienzyme Ribonuclease Complex / Q000235:genetics*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics*; D012720:Severity of Illness Index; D013116:Spinal Cord / Q000473:pathology*
chemical_list: C571397:EXOSC3 protein, human; D016601:RNA-Binding Proteins; D063326:Exosome Multienzyme Ribonuclease Complex
references.citation: Cell. 2006 Dec 15;127(6):1223-37
references.pmid: 17174896
references.citation: EMBO J. 2010 Jul 21;29(14):2342-57
references.pmid: 20531386
references.citation: Neurology. 2010 Oct 19;75(16):1459-64
references.pmid: 20956791
references.citation: Acta Neuropathol. 2011 May;121(5):671-3
references.pmid: 21468723
references.citation: Brain. 2011 Jan;134(Pt 1):143-56
references.pmid: 20952379
references.citation: Nat Genet. 2012 Apr 29;44(6):704-8
references.pmid: 22544365
references.citation: Eur J Paediatr Neurol. 2008 Mar;12(2):97-101
references.pmid: 17681808
references.citation: Curr Opin Struct Biol. 2008 Dec;18(6):709-13
references.pmid: 18955140
references.citation: Nucleic Acids Res. 2008 Dec;36(21):6645-55
references.pmid: 18940861
references.citation: Brain Dev. 1993 Nov-Dec;15(6):411-22
references.pmid: 8147499
references.citation: Neurology. 2013 Jan 29;80(5):438-46
references.pmid: 23284067
references.citation: Biochem Biophys Res Commun. 2012 Jul 6;423(3):461-6
references.pmid: 22668878
references.citation: J Inherit Metab Dis. 2011 Dec;34(6):1225-7
references.pmid: 21826524
references.citation: J Mol Biol. 2002 Nov 1;323(4):653-63
references.pmid: 12419256
references.citation: Biochem Soc Trans. 2012 Aug;40(4):850-5
references.pmid: 22817747
references.citation: J Biol Chem. 2010 Feb 5;285(6):3540-3547
references.pmid: 19955569
references.citation: Am J Med Genet A. 2003 Feb 15;117A(1):10-7
references.pmid: 12548734
references.citation: Genome Res. 2004 Jul;14(7):1315-23
references.pmid: 15231747
references.citation: Orphanet J Rare Dis. 2011 Jul 12;6:50
references.pmid: 21749694
references.citation: RNA. 2011 Jan;17(1):1-13
references.pmid: 21068185
references.citation: Muscle Nerve. 2010 Jan;41(1):5-17
references.pmid: 19697368
references.citation: Neuroradiology. 1994 Jul;36(5):364-8
references.pmid: 7936176
references.citation: Am J Hum Genet. 2009 Aug;85(2):281-9
references.pmid: 19646678