Clinical translation of genetic testing in TTR Amyloidosis: genotype-phenotype correlations, management of asymptomatic carriers and familial screening

Abstract

Transthyretin (TTR)-related amyloidosis (ATTR) is a heterogeneous disease with different organ involvement depending on the type of TTR infiltration [mutated (vTTR) or wild-type (wtTTR)]. Genetic testing in ATTR is required to define diagnosis and identify asymptomatic at-risk family members. Since new therapies are maximally effective in the early stages of the disease, there is a growing agreement about the need for close monitoring of genotype-positive, phenotype-negative individuals to assure a prompt treatment when minor disease signs are detected. This review summarizes the complexity of genotype-phenotype correlation and revises the current indications with respect to familiar screening and management of asymptomatic carriers.

Keywords

Cardiac amyloidosis / transthyretin amyloidosis / genetic testing / genotype-phenotype correlations / familiar screening

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