Search: (L773:1460 2083 OR L773:1460 2083 OR L773:0964 6906) srt2:(1995-1999) >
Missense mutations ...
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Dahl, NiklasUppsala universitet,Institutionen för genetik och patologi
(author)
Missense mutations in the human glutathione synthetase gene result in severe metabolic acidosis, 5-oxoprolinuria, hemolytic anemia and neurological dysfunction
- Article/chapterEnglish1997
Publisher, publication year, extent ...
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Oxford University Press (OUP),1997
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-52132
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-52132URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:1956749URI
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https://doi.org/10.1093/hmg/6.7.1147DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Severe glutathione synthetase (GS) deficiency is a rare genetic disorder with neonatal onset. The enzymatic block of the gamma-glutamyl cycle leads to a generalized glutathione deficiency. Clinically affected patients present with severe metabolic acidosis, 5-oxoprolinuria, increased rate of hemolysis and defective function of the central nervous system. The disorder is inherited in an autosomal recessive mode and, until recently, the molecular basis has remained unknown. We have sequenced 18 GS alleles associated with enzyme deficiency and we detected missense mutations by direct sequencing of cDNAs and genomic DNA. In total, 13 different mutations were identified. Four patients were found to be compound heterozygotes and two individuals were apparently homozygous. Reduced enzymatic activities were demonstrated in recombinant protein expressed from cDNAs in four cases with different missense mutations. The results from biochemical analysis of patient specimens, supported by the properties of the expressed mutant proteins, indicate that a residual activity is present in affected individuals. Our results suggest that complete loss of function of both GS alleles is probably lethal. It is postulated that missense mutations will account for the phenotype in the majority of patients with severe GS deficiency.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Pigg, MarittaUppsala universitet,Institutionen för genetik och patologi
(author)
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Ristoff, E.Karolinska Institutet
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Gali, R.
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Carlsson, B.
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Mannervik, B.
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Larsson, A.Karolinska Institutet
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Board, P.
(author)
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Uppsala universitetInstitutionen för genetik och patologi
(creator_code:org_t)
Related titles
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In:Human Molecular Genetics: Oxford University Press (OUP)6:7, s. 1147-11520964-69061460-2083
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