Transfection screening for primary defects in the pyruvate dehydrogenase E1alpha subunit gene |
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Authors: | Brown RM; Otero LJ; Brown GK |
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Institution: | Department of Biochemistry, University of Oxford, UK. |
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Abstract: | In a significant number of patients with biochemical evidence of a defect
in the E1 (pyruvate dehydrogenase) 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 E1alpha subunit gene (which is
responsible for the great majority of defined cases of pyruvate
dehydrogenase deficiency), we have developed a method to screen for E1alpha
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 E1alpha 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.
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