Identification of a novel non-amyloidogenic transthyretin polymorphism (His 74) in the German population

Abstract

We examined the transthyretin gene of a German individual by direct DNA sequencing and found a guanine to cytosine transversion at the first base ofcodon 74 which resulted in a replacement ofhistidinefor aspartic acid. This mutation was confirmed by restriction fragment length polymorphism analysis using the polymerase chain reaction and the variant protein was proven to exist in plasma by sequence analysis of purified transthyretin. This variant transthyretin which was found in 7 of 4000 individuals by isoelectric focusing gel analysis is considered to be a relatively common polymorphism in the German population. None of the 7 individuals has a family history of amyloidosis or thyroid disorder.

Key Words:

• Transthyretin
• Amyloid
• Amyloidosis
• German
• Polymorphism
• Mutation