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Refined localization of the pyruvate dehydrogenase E1 alpha gene (PDHA1) by linkage analysis.

Pyruvate dehydrogenase (PDH) E1 alpha is a key component in the PDH complex which catalyzes the oxidative decarboxylation of pyruvate to acetyl-CoA. Defects in the gene coding for PDH E1 alpha (PDHA1) are associated with a variety of clinical symptoms, often of a severe character. In the present study, the segregation of three polymorphic CA repeats located in PDHA1 was followed in the 40 CEPH reference pedigrees. Using these data, multipoint linkage analysis was carried out, refining the genetic location of PDHA1. The 16-point map presented locates PDHA1 in an approximately 3-cM interval between DXS999 and DXS365 with odds of more than 1000:1. From known physical localizations of the flanking marker loci, PDHA1 could be regionally assigned to Xp22.1-p22.2. The information provided should be of value in clinical settings.