000151660 001__ 151660
000151660 005__ 20250415100045.0
000151660 0247_ $$2pmc$$apmc:PMC7383914
000151660 0247_ $$2doi$$a10.1002/ana.25723
000151660 0247_ $$2ISSN$$a0364-5134
000151660 0247_ $$2ISSN$$a1531-8249
000151660 0247_ $$2altmetric$$aaltmetric:78458360
000151660 0247_ $$2pmid$$apmid:32219868
000151660 037__ $$aDZNE-2020-01239
000151660 041__ $$aEnglish
000151660 082__ $$a610
000151660 1001_ $$00000-0002-0666-4380$$aCaporali, Leonardo$$b0
000151660 245__ $$aATPase Domain AFG3L2 Mutations Alter OPA1 Processing and Cause Optic Neuropathy
000151660 260__ $$aHoboken, NJ$$bWiley-Blackwell$$c2020
000151660 3367_ $$2DRIVER$$aarticle
000151660 3367_ $$2DataCite$$aOutput Types/Journal article
000151660 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1744700772_4060
000151660 3367_ $$2BibTeX$$aARTICLE
000151660 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000151660 3367_ $$00$$2EndNote$$aJournal Article
000151660 520__ $$aObjectiveDominant optic atrophy (DOA) is the most common inherited optic neuropathy, with a prevalence of 1:12,000 to 1:25,000. OPA1 mutations are found in 70% of DOA patients, with a significant number remaining undiagnosed.MethodsWe screened 286 index cases presenting optic atrophy, negative for OPA1 mutations, by targeted next generation sequencing or whole exome sequencing. Pathogenicity and molecular mechanisms of the identified variants were studied in yeast and patient‐derived fibroblasts.ResultsTwelve cases (4%) were found to carry novel variants in AFG3L2, a gene that has been associated with autosomal dominant spinocerebellar ataxia 28 (SCA28). Half of cases were familial with a dominant inheritance, whereas the others were sporadic, including de novo mutations. Biallelic mutations were found in 3 probands with severe syndromic optic neuropathy, acting as recessive or phenotype‐modifier variants. All the DOA‐associated AFG3L2 mutations were clustered in the ATPase domain, whereas SCA28‐associated mutations mostly affect the proteolytic domain. The pathogenic role of DOA‐associated AFG3L2 mutations was confirmed in yeast, unraveling a mechanism distinct from that of SCA28‐associated AFG3L2 mutations. Patients' fibroblasts showed abnormal OPA1 processing, with accumulation of the fission‐inducing short forms leading to mitochondrial network fragmentation, not observed in SCA28 patients' cells.InterpretationThis study demonstrates that mutations in AFG3L2 are a relevant cause of optic neuropathy, broadening the spectrum of clinical manifestations and genetic mechanisms associated with AFG3L2 mutations, and underscores the pivotal role of OPA1 and its processing in the pathogenesis of DOA. ANN NEUROL 2020 ANN NEUROL 2020;88:18–32
000151660 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x0
000151660 536__ $$0G:(DE-HGF)POF3-345$$a345 - Population Studies and Genetics (POF3-345)$$cPOF3-345$$fPOF III$$x1
000151660 588__ $$aDataset connected to CrossRef
000151660 650_2 $$2MeSH$$aATP-Dependent Proteases: genetics
000151660 650_2 $$2MeSH$$aATPases Associated with Diverse Cellular Activities: genetics
000151660 650_2 $$2MeSH$$aAdolescent
000151660 650_2 $$2MeSH$$aAdult
000151660 650_2 $$2MeSH$$aAged
000151660 650_2 $$2MeSH$$aChild
000151660 650_2 $$2MeSH$$aFemale
000151660 650_2 $$2MeSH$$aGTP Phosphohydrolases: genetics
000151660 650_2 $$2MeSH$$aGenetic Testing
000151660 650_2 $$2MeSH$$aHigh-Throughput Nucleotide Sequencing
000151660 650_2 $$2MeSH$$aHumans
000151660 650_2 $$2MeSH$$aMale
000151660 650_2 $$2MeSH$$aMiddle Aged
000151660 650_2 $$2MeSH$$aMutation
000151660 650_2 $$2MeSH$$aOptic Atrophy: genetics
000151660 650_2 $$2MeSH$$aOptic Nerve Diseases: genetics
000151660 650_2 $$2MeSH$$aPedigree
000151660 650_2 $$2MeSH$$aExome Sequencing
000151660 650_2 $$2MeSH$$aYoung Adult
000151660 7001_ $$aMagri, Stefania$$b1
000151660 7001_ $$aLegati, Andrea$$b2
000151660 7001_ $$aDel Dotto, Valentina$$b3
000151660 7001_ $$aTagliavini, Francesca$$b4
000151660 7001_ $$aBalistreri, Francesca$$b5
000151660 7001_ $$aNasca, Alessia$$b6
000151660 7001_ $$aLa Morgia, Chiara$$b7
000151660 7001_ $$aCarbonelli, Michele$$b8
000151660 7001_ $$aValentino, Maria L.$$b9
000151660 7001_ $$aLamantea, Eleonora$$b10
000151660 7001_ $$aBaratta, Silvia$$b11
000151660 7001_ $$0P:(DE-2719)2810795$$aSchöls, Ludger$$b12$$udzne
000151660 7001_ $$0P:(DE-2719)2812018$$aSchüle, Rebecca$$b13$$udzne
000151660 7001_ $$aBarboni, Piero$$b14
000151660 7001_ $$aCascavilla, Maria L.$$b15
000151660 7001_ $$aMaresca, Alessandra$$b16
000151660 7001_ $$aCapristo, Mariantonietta$$b17
000151660 7001_ $$aArdissone, Anna$$b18
000151660 7001_ $$00000-0001-6854-765X$$aPareyson, Davide$$b19
000151660 7001_ $$aCammarata, Gabriella$$b20
000151660 7001_ $$aMelzi, Lisa$$b21
000151660 7001_ $$aZeviani, Massimo$$b22
000151660 7001_ $$aPeverelli, Lorenzo$$b23
000151660 7001_ $$aLamperti, Costanza$$b24
000151660 7001_ $$aMarzoli, Stefania B.$$b25
000151660 7001_ $$00000-0001-7185-6445$$aFang, Mingyan$$b26
000151660 7001_ $$0P:(DE-2719)2811275$$aSynofzik, Matthis$$b27$$udzne
000151660 7001_ $$00000-0002-6564-3766$$aGhezzi, Daniele$$b28
000151660 7001_ $$aCarelli, Valerio$$b29
000151660 7001_ $$00000-0002-2420-5233$$aTaroni, Franco$$b30
000151660 773__ $$0PERI:(DE-600)2037912-2$$a10.1002/ana.25723$$gVol. 88, no. 1, p. 18 - 32$$n1$$p18 - 32$$tAnnals of neurology$$v88$$x1531-8249$$y2020
000151660 8564_ $$uhttps://onlinelibrary.wiley.com/doi/full/10.1002/ana.25723
000151660 8564_ $$uhttps://pub.dzne.de/record/151660/files/DZNE-2020-01239.pdf$$yOpenAccess
000151660 8564_ $$uhttps://pub.dzne.de/record/151660/files/DZNE-2020-01239.pdf?subformat=pdfa$$xpdfa$$yOpenAccess
000151660 909CO $$ooai:pub.dzne.de:151660$$popenaire$$popen_access$$pVDB$$pdriver$$pdnbdelivery
000151660 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2810795$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b12$$kDZNE
000151660 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2812018$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b13$$kDZNE
000151660 9101_ $$0I:(DE-588)1065079516$$6P:(DE-2719)2811275$$aDeutsches Zentrum für Neurodegenerative Erkrankungen$$b27$$kDZNE
000151660 9131_ $$0G:(DE-HGF)POF3-344$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vClinical and Health Care Research$$x0
000151660 9131_ $$0G:(DE-HGF)POF3-345$$1G:(DE-HGF)POF3-340$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lErkrankungen des Nervensystems$$vPopulation Studies and Genetics$$x1
000151660 9141_ $$y2020
000151660 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2020-02-26
000151660 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2022-11-30
000151660 915__ $$0LIC:(DE-HGF)CCBYNCND4$$2HGFVOC$$aCreative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0
000151660 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bANN NEUROL : 2021$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)9910$$2StatID$$aIF >= 10$$bANN NEUROL : 2021$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)3001$$2StatID$$aDEAL Wiley$$d2020-02-26$$wger
000151660 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)0510$$2StatID$$aOpenAccess
000151660 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2020-02-26
000151660 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2022-11-30
000151660 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz$$d2022-11-30$$wger
000151660 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2022-11-30
000151660 9201_ $$0I:(DE-2719)1210000$$kAG Gasser$$lParkinson Genetics$$x0
000151660 9201_ $$0I:(DE-2719)5000024$$kAG Maetzler$$lFunctional Neurogeriatrics$$x1
000151660 980__ $$ajournal
000151660 980__ $$aVDB
000151660 980__ $$aUNRESTRICTED
000151660 980__ $$aI:(DE-2719)1210000
000151660 980__ $$aI:(DE-2719)5000024
000151660 9801_ $$aFullTexts