Molecular detection of carriers of hereditary amyloidosis in a Swedish-American family.

Autosomal dominant amyloidosis, also known as familial amyloidotic polyneuropathy (FAP), is a late-onset disorder associated with variants of the protein prealbumin. In FAP Type I, the variant contains a single amino acid substitution at position 30 in the subunit. This substitution corresponds to a single base change in the gene, coincidentally creating a new site for the restriction enzyme NsiI. This change is detectable in the DNA of gene carriers with restriction fragment length polymorphism (RFLP) methods. A well-characterized American family of Swedish origin was studied by this method using a prealbumin cDNA. The RFLP data were found to correlate with previous biochemical characterization of the prealbumin in this family, indicating that this test represents a reliable way to directly detect the DNA mutation responsible for the condition. This test can be used for preclinical diagnosis of gene carriers, including prenatal diagnosis.