IDENTIFICATION OF A NOVEL NON-AMYLOIDOGENIC TRANSTHYRETIN POLYMORPHISM (HIS-74) IN THE GERMAN POPULATION

We examined the transthyretin gene of a German individual by direct DN A sequencing and found a guanine to cytosine transversion at the first base of codon 74 which resulted in a replacement of histidine for asp artic acid. This mutation was confirmed by restriction fragment length polymorphism analysis using the polymerase chain reaction and the var iant protein was proven to exist in plasma by sequence analysis of pur ified transthyretin. This variant transthyretin which was found in 7 o f 4000 individuals by isoelectricfocusing gel analysis is considered t o be a relatively common polymorphism in the German population. None o f the 7 individuals has a family history of amyloidosis or thyroid dis order.