Transthyretin mutations in hyperthyroxinemia and amyloid diseases

Over 80 different disease causing mutations in transthyretin (TTR) have bee n reported. The vast majority are inherited in an autosomal dominant manner and are related to amyloid deposition, affecting predominantly peripheral nerve and/or the heart. A small portion of TTR mutations are apparently non amyloidogenic. Among these are mutations responsible for hyperthyroxinemia , presenting high affinity for thyroxine (a TTR ligand), Compound heterozyg otic individuals for TTR mutants have been described; noteworthy is the cli nically protective effect exerted by a non pathogenic over a pathogenic mut ation. Current TTR mutations and their significance are briefly reviewed he re. Hum Mutat 17:493-503, 2001. (C) 2001 Wiley-Liss, Inc.