Publication:
Clinically distinct phenotypes of canavan disease correlate with residual aspartoacylase enzyme activity

dc.contributor.coauthorMendes, Marisa I.
dc.contributor.coauthorSmith, Desirée E.C.
dc.contributor.coauthorPop, Ana
dc.contributor.coauthorLennertz, Pascal
dc.contributor.coauthorFernandez Ojeda, Matilde R.
dc.contributor.coauthorKanhai, Warsha A.
dc.contributor.coauthorvan Dooren, Silvy J.M.
dc.contributor.coauthorAnikster, Yair
dc.contributor.coauthorBarić, Ivo
dc.contributor.coauthorBoelen, Caroline
dc.contributor.coauthorCampistol, Jaime
dc.contributor.coauthorde Boer, Lonneke
dc.contributor.coauthorKariminejad, Ariana
dc.contributor.coauthorRoubertie, Agathe
dc.contributor.coauthorVerbruggen, Krijn T.
dc.contributor.coauthorVianey-Saban, Christine
dc.contributor.coauthorWilliams, Monique
dc.contributor.coauthorSalomons, Gajja S.
dc.contributor.departmentSchool of Medicine
dc.contributor.kuauthorKayserili, Hülya
dc.contributor.schoolcollegeinstituteSCHOOL OF MEDICINE
dc.date.accessioned2024-11-09T23:52:22Z
dc.date.issued2017
dc.description.abstractWe describe 14 patients with 12 novel missense mutations in ASPA, the gene causing Canavan disease (CD). We developed a method to study the effect of these 12 variants on the function of aspartoacylase—the hydrolysis of N-acetyl-l-aspartic acid (NAA) to aspartate and acetate. The wild-type ASPA open reading frame (ORF) and the ORFs containing each of the variants were transfected into HEK293 cells. Enzyme activity was determined by incubating cell lysates with NAA and measuring the released aspartic acid by LC–MS/MS. Clinical data were obtained for 11 patients by means of questionnaires. Four patients presented with a non-typical clinical picture or with the milder form of CD, whereas seven presented with severe CD. The mutations found in the mild patients corresponded to the variants with the highest residual enzyme activities, suggesting that this assay can help evaluate unknown variants found in patients with atypical presentation. We have detected a correlation between clinical presentation, enzyme activity, and genotype for CD.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue5
dc.description.openaccessYES
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.volume38
dc.identifier.doi10.1002/humu.23181
dc.identifier.issn1059-7794
dc.identifier.scopus2-s2.0-85013055763
dc.identifier.urihttps://doi.org/10.1002/humu.23181
dc.identifier.urihttps://hdl.handle.net/20.500.14288/14848
dc.keywordsCanavan disease
dc.keywordsASPA
dc.keywordsASPA activity
dc.keywordsMissense variants
dc.keywordsClinical phenotype
dc.keywordsFunctional assay
dc.language.isoeng
dc.publisherWiley
dc.relation.ispartofHuman Mutation
dc.subjectGenetics
dc.subjectHeredity
dc.titleClinically distinct phenotypes of canavan disease correlate with residual aspartoacylase enzyme activity
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorKayserili, Hülya
local.publication.orgunit1SCHOOL OF MEDICINE
local.publication.orgunit2School of Medicine
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