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