Clinically Distinct Phenotypes of Canavan Disease Correlate with Residual Aspartoacylase Enzyme Activity
Publication year
2017Source
Human Mutation, 38, 5, (2017), pp. 524-531ISSN
Publication type
Article / Letter to editor

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Organization
Paediatrics
Paediatrics - OUD tm 2017
Journal title
Human Mutation
Volume
vol. 38
Issue
iss. 5
Page start
p. 524
Page end
p. 531
Subject
Radboudumc 6: Metabolic Disorders RIMLS: Radboud Institute for Molecular Life SciencesAbstract
We 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.
This item appears in the following Collection(s)
- Academic publications [204859]
- Electronic publications [103204]
- Faculty of Medical Sciences [81031]
- Open Access publications [71761]
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