TTR exon scanning in peripheral neuropathies

Transthyretin (TTR) is a plasma protein in which most of the coding region is constituted of three exons, each one of approximately 200 bp. Several TTR variants have been reported in association with familial amyloid polyneuropathy (FAP) and the characterization of the mutations is crucial for understanding the process of amyloidogenesis. In order to simplify mutation screening and DNA sequencing studies, a method of exon scanning was developed employing duplex amplification of exon 2/3 and individual amplification of exon 4 followed by single strand conformation polymorphism analysis (SSCPs) on acrylamide gels and silver staining. In this work, 22 different known TTR mutations were discriminated and studies on 210 samples from patients with peripheral neuropathies detected one polymorphic mutation (TTR Ser 6), TTR Asn 90, found previously in the normal Portuguese and German populations, and three other mutations, one of them TTR Ala 60.