Description genetic mutations

Goyette R et al, Severe and mild mutations in cis for the methylenetetrahydrofolate reductase (MTHFR) gene, and description of five novel mutations in MTHFR, Am J Hum Genet 1996 59(6) 1268-1275. 

Most early clinical descriptions of apparent thiamine-responsive PDC deficiency were not characterized biochemically to ascertain true thiamine dependence. In subsequent reports, immunochemical analyses have demonstrated varied patterns of a- and P-subunit expression, and in vitro studies of cultured cells have sometimes found altered El enzyme kinetics (high Km, low Vmax) for TPP. When molecular genetic analyses have been undertaken, different mutations have been identified within the conserved TPP-binding motif that are considered to lead to diminished binding affinity for TPP or to decreased stability of the oc2P2 tetramer. 

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