Hereditary transthyretin amyloidosis

In this chapter we discuss what is known about the physiological role of transthyretin and which are the key mechanisms underlying transthyretin fibrillogenesis in vivo. More than 130 amyloidogenic mutations of the TTR gene have been described. Mutations destabilize the native protein structure promoting misfolding and dissociation into monomeric species that aggregate and ultimately deposit in different tissues and organs. The complex genotype-phenotype relationship that characterizes hereditary transthyretin amyloidosis (ATTRv) is discussed and the main clinical findings that can raise disease suspicion across different populations are highlighted.