A novel gross deletion caused by non-homologous recombination of the PDHX gene in a patient with pyruvate dehydrogenase deficiency.

[pyruvate dehydrogenase deficiency]

We report here the molecular analysis of a pyruvate dehydrogenase E 3 -binding protein (PDH -E 3 BP ) deficiency in a new patient , born to first cousin parents . She has initially presented with a non-progressive and unspecific encephalopathy , followed by an acute neurological deterioration at 14 years of age . E 3 BP subunit was undetectable on Western blot . The sequence of exons 1 -9 and exon 11 of the PDHX gene were normal , but exon 10 was impossible to amplify with standard PCR . Long -range PCR including exons 9 -11 (11 .5 kb ) was performed . The patient 's sample displayed a unique PCR product of 7 .5 kb , whereas the parents ' samples displayed two bands (11 .5 and 7 .5 kb ). The deletion breakpoints were determined by restriction analysis followed by direct sequencing . The homozygous deletion covered the end of intron 9 , exon 10 and the beginning of intron 10 and was found to be 3913 bp long . The cDNA sequencing confirmed the deletion of exon 10 . The most probable mechanism for this gross deletion appears to be a slipped mispairing mediated by an exact direct repeat CCACTG . It is the first time that a non-homologous recombination is reported in the PDHX gene causing pyruvate dehydrogenase complex (PDHc ) deficiency .

Diseases
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Diseases presenting "followed by an acute neurological deterioration at 14 years of age" symptom

pyruvate dehydrogenase deficiency

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