Hereditary Amyloidosis: Insights Into a Fibrinogen A Variant Protein

Abstract

Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly intissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determineits nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here wereport the precise diagnosis and explored the possible reasons of the structural pathogenicity for a renal amyloidosis related toa fibrinogen Aα-chain variant. Whole-exome sequencing and GATK calling pipeline were leveraged to characterize the proteinvariant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of thevariants aggregation. Our pipeline allowed the identification of a single-point variant of fibrinogen Aα-chain, which opened thepossibility of curative transplantation. In silico structural analysis suggested that the pathogenicity of the variant may be attrib-uted to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a β-sheet structure. Exploiting the com-prehensive coverage of whole-genome sequencing, we managed to fill a vacant stage in the diagnosis of hereditary amyloidosisand to stimulate the advancement in biomedicine.