Journal Article

Transfection Screening for Primary Defects in the Pyruvate Dehydrogenase E1α Subunit Gene

Ruth M. Brown, Lucy J. Otero and Garry K. Brown

in Human Molecular Genetics

Volume 6, issue 8, pages 1361-1367
Published in print August 1997 | ISSN: 0964-6906
Published online August 1997 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/6.8.1361
Transfection Screening for Primary Defects in the Pyruvate Dehydrogenase E1α Subunit Gene

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In a significant number of patients with biochemical evidence of a defect in the E1 (pyruvate dehydro-genase) component of the pyruvate dehydrogenase complex, it has not proved possible to identify a mutation in the gene coding regions. To assess the need for more extensive genetic analysis in these patients and to establish a test system in which to study the biochemical consequences of mutations in the E1α subunit gene (which is responsible for the great majority of defined cases of pyruvate dehydrogenase deficiency), we have developed a method to screen for E1α gene defects based on complementation of the enzyme deficiency in transformed fibroblast cell lines following transfection and expression of the normal cDNA. Using this system, cell lines from patients with a variety of different defined mutations in the E1α gene show restoration of enzyme activity. A number of patients have been identified in whom deficient enzyme activity is not restored by expression of the normal cDNA indicating that an alternative explanation for the enzyme defect must be sought.

Journal Article.  5633 words.  Illustrated.

Subjects: Genetics and Genomics

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