AN INHERITED NON-AMYLOIDOGENIC TRANSTHYRETIN VARIANT, [SER6]-TTR, WITH INCREASED THYROXINE-BINDING AFFINITY, CHARACTERIZED BY DNA SEQUENCING

Amplification and sequencing of the four transthyretin (TTR) exons of a subject with a variant TTR with four-fold increased affinity for thyroxine revealed a heterozygous G to A point mutation at base 7 of exon 2. This results in a serine for glycine change at residue 6 of the mature TTR monomer. No other mutations were found in any exon. Amplification and MspI digestion of TTR exon 2 from the leucocyte DNA of eight members of the subject's family revealed that all but one member were also heterozygous for [Ser6]-TTR.