Diagnosis of Maryland/German familial amyloidotic polyneuropathy using allele-specific, enzymatically amplified, genomic DNA.

Diagnoses of familial amyloidotic polyneuropathies have been traditionally based on attempts to distinguish clinical features and ancestry or geographic origin of cases. Most are associated with extracellular deposition of a variant prealbumin (also known as transthyretin). Recent molecular studies demonstrated eight distinct amyloid-associated point mutations in the prealbumin gene on the long arm of chromosome 18 that are associated with hereditary amyloidosis. These findings provide for means of diagnosis using recombinant DNA methods. In a family with the Maryland/German type of familial amyloidotic polyneuropathy, the proband and 2 of 5 at-risk offspring were diagnosed using the polymerase chain reaction. Allele-specific enzymatic amplification of genomic DNA demonstrated the histidine-58 variant prealbumin gene. This study confirms the point mutation of the prealbumin gene as a cause for this type of familial amyloidotic polyneuropathy. Preclinical diagnosis illustrates the potential for development of treatment strategies prior to disease onset.