Transthyretin mutations in hyperthyroxinemia and amyloid diseases

Over 80 different disease‐causing mutations in transthyretin (TTR) have been 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 heterozygotic individuals for TTR mutants have been described; noteworthy is the clinically protective effect exerted by a non‐pathogenic over a pathogenic mutation. Current TTR mutations and their significance are briefly reviewed here. Hum Mutat 17:493–503, 2001. © 2001 Wiley‐Liss, Inc.