A mutation in apolipoprotein A-I in the Iowa type of familial amyloidotic polyneuropathy.

Immunoblotting of isoelectric focusing gels of plasma and direct genomic DNA sequencing have been used to characterize a mutation in apolipoprotein A-I associated with the familial amyloidotic polyneuropathy originally described by Van Allen in an Iowa kindred. An arginine for glycine substitution in apolipoprotein A-I identified in the proband's amyloid fibrils was determined to be the result of a mutation of guanine to cytosine in the apolipoprotein A-I gene at the position corresponding to the first base of codon 26. Direct sequencing of genomic DNA of three affected individuals who died in the 1960s confirmed the inheritance of the disorder. Immunoblot analysis detected the variant apolipoprotein A-I in the proband's plasma and in several at-risk members of the kindred. In addition, allele-specific amplification by the polymerase chain reaction was used to detect carriers of the variant gene.