ABERRANT SPLICING OF EXON-6 IN THE PYRUVATE DEHYDROGENASE-E1-ALPHA MESSENGER-RNA LINKED TO A SILENT MUTATION IN A LARGE FAMILY WITH LEIGH ENCEPHALOMYELOPATHY

Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha. deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of ''malaises.'' In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.