Transthyretin gene mutation

The structure of transthyretin. The molecule contains eight antiparallel A-strands (A-H) arranged in two parallel planes. The circulating form of transthyretin is a tetramer. Some mutations in the transthyretin gene are associated with amyloidosis and eight of the amino acid alterations causing this disease are indicated. In plasma, transthyretin is a tetramer composed of identical monomers. It appears that mutations cause the monomeric unfolded intermediate of transthyretin to aggregate into an insoluble A-amyloid fibril formation. 

Transthyretin amyloidosis (also called familial amyloid polyneuropathy) is an autosomal dominant syndrome characterized by peripheral neuropathy. This disease results from one of five mutations identified thus far in the gene for transthyretin. Transthyretin is also called prealbumin (although it has no structural relationship to albumin) because it migrates ahead of albumin in standard electrophoresis at pH 8.6. Transthyretin is synthesized in the liver and is a normal plasma protein with a concentration of 20-40 mg/dL. It transports thyroxine and retinol binding protein (Chapter 38). The concentration of transthyretin is significantly decreased in malnutrition and plasma levels are diagnostic of disorders of malnutrition (Chapter 17). 

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