Hereditary Transthyretin-Related Amyloidosis: Genetic Heterogeneity and Early Personalized Gene Therapy

Abstract

Point mutations of the transthyretin (TTR) gene are related with hereditary amyloidosis (hATTR). The number of people affected by this rare disease is only partially estimated. The real impact of somatic mosaicism and other genetic factors on expressivity, complexity, progression, and transmission of the disease should be better investigated. The relevance of this rare disease is increasing and many efforts have been made to improve the time to diagnosis and to estimate the real number of cases in endemic and non-endemic areas. In this context, somatic mosaicism should be better investigated to explain the complexity of the heterogeneity of the hATTR clinical features, to better estimate the number of new cases, and to focus on early and personalized gene therapy. Gene therapy can potentially improve the living conditions of affected individuals and is one of the central goals in research on amyloidosis related to the TTR gene, with the advantage of overcoming liver transplantation as the sole treatment for hATTR disease.

Case Report: Transthyretin Glu54Leu—a rare mutation with predominant cardiac phenotype

“…Broad intra and interfamilial variations in terms of age of onset and severity have been observed in ATTRv amyloidosis, caused by diverse mutations. Therefore, we can speculate that genetic modifiers and epigenetic factors are causing such variability (21,22). Future research should be conducted to reach more definitive conclusions.…”