Functional characterization of missense variants in the creatine transporter gene (SLC6A8): improved diagnostic application.
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Publication year
2007Source
Human Mutation, 28, 9, (2007), pp. 890-6ISSN
Publication type
Article / Letter to editor
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Organization
Human Genetics
Journal title
Human Mutation
Volume
vol. 28
Issue
iss. 9
Page start
p. 890
Page end
p. 6
Subject
DCN 2: Functional Neurogenomics; IGMD 3: Genomic disorders and inherited multi-system disorders; UMCN 5.1: Genetic defects of metabolismAbstract
Creatine transporter deficiency is an X-linked mental retardation disorder caused by mutations in the creatine transporter gene (SLC6A8). So far, 20 mutations in the SLC6A8 gene have been described. We have developed a diagnostic assay to test creatine uptake in fibroblasts. Additionally, we expanded the assay to characterize novel SLC6A8 missense variants. A total of 13 variants were introduced in the SLC6A8 cDNA by site-directed mutagenesis. All variants were transiently transfected in SLC6A8-deficient fibroblasts and tested for restoration of creatine uptake in deficient primary fibroblasts. Thus, we proved that nine variants (p.Gly87Arg, p.Phe107del, p.Tyr317X, p.Asn336del, p.Cys337Trp, p.Ile347del, p.Pro390Leu, p.Arg391Trp, and p.Pro554Leu) are pathogenic mutations and four variants (p.Lys4Arg, p.Gly26Arg, p.Met560Val, and p.Val629Ile) are nonpathogenic. The present study provides an improved diagnostic tool to classify sequence variants of unknown significance.
This item appears in the following Collection(s)
- Academic publications [238430]
- Electronic publications [122512]
- Faculty of Medical Sciences [90359]
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