Prenatal detection of a gene for hereditary amyloidosis.

ABSTRACT

Autosomal dominant amyloidosis of the Indiana/Swiss type (familial amyloidotic polyneuropathy type II) is a late-onset disorder characterized by carpal tunnel syndrome, peripheral neuropathy, vitreous opacities, and cardiomyopathy. The genetic basis of the disease is a variant of plasma prealbumin (transthyretin) which has a serine for isoleucine substitution at amino acid 84 of the 127 residue prealbumin molecule. Using the polymerase chain reaction (PCR), we amplified exon 3 of the prealbumin gene in DNA extracted from amniocytes of a fetus at-risk of carrying the serine-84 prealbumin gene. By allele-specific oligonucleotide analysis as well as restriction enzyme analysis of the amplification products it was determined that the fetus was a carrier of the serine-84 variant gene. This finding was confirmed at birth by Southern blot analysis using DNA obtained from cord blood. This is the first report of the prenatal detection of a gene for hereditary amyloidosis.