Acute intermittent porphyria: novel missense mutations in the human hydroxymethylbilane synthase gene

To identify mutations in families with acute intermittent porphyria, an autosomal dominant inborn error of metabolism that results from the half-normal activity of the third enzyme in the heme biosynthetic pathway, hydroxymethylbilane synthase.

Mutations were identified by direct solid phase sequencing.

Two novel missense mutations E80G and T78P and three previously reported mutations, R173W, G111R, and the splice site lesion, IVS1+1, were detected, each in an unrelated proband. The causality of the novel missense mutations was demonstrated by expression studies.

These findings provide for the precise diagnosis of carriers in these families and further expand the molecular heterogeneity of AIP.