title: Diagnostics in patients with glutathione synthetase deficiency but without mutations in the exons of the GSS gene.
abstract: The synthesis of the ubiquitous tripeptide glutathione is impaired in patients with glutathione synthetase deficiency. The defect is inherited in an autosomal recessive manner, and the diagnosis is based on clinical, biochemical, and genetic criteria. In seven of our 30 index cases, however, no disease causing mutations could be identified in the coding exons or exon-intron boundaries of the glutathione synthetase gene GSS. These patients had severely decreased glutathione synthetase activities in lysates of cultured fibroblasts, and the levels of the enzyme were undetectable using a polyclonal antibody raised against human glutathione synthetase. RT-PCR mediated sequence analysis revealed previously not reported splice mutations in all patients. Thus, we conclude that in the investigation of patients with glutathione synthetase deficiency, and probably other genetic diseases as well, it might be time saving to initiate mutation analysis with sequencing of mRNA.
authors.affiliation: Department of Clinical Science, Division of Pediatrics, Karolinska Institutet, Huddinge University H-ospital, 141 86 Stockholm, Sweden. runa.njalsson@mednut.ki.se
authors.forename: Runa
authors.initials: R
authors.lastname: Njålsson
authors.forename: Katarina
authors.initials: K
authors.lastname: Carlsson
authors.forename: Andreas
authors.initials: A
authors.lastname: Winkler
authors.forename: Agne
authors.initials: A
authors.lastname: Larsson
authors.forename: Svante
authors.initials: S
authors.lastname: Norgren
mesh_terms: D015153:Blotting, Western; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005981:Glutathione Synthase / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008661:Metabolism, Inborn Errors / Q000175:diagnosis* / Q000201:enzymology* / Q000235:genetics; D009154:Mutation
chemical_list: D018076:DNA, Complementary; D004247:DNA; D005981:Glutathione Synthase