Structure of ATTRv-F64S fibrils isolated from skin tissue of a living patient

TL;DR

Researchers determined the structure of amyloid fibrils from a patient's skin, supporting skin biopsies as a non-invasive diagnostic method for a rare disease.

Contribution

The study presents the cryo-EM structure of transthyretin fibrils from a living patient with a rare F64S mutation, validating skin biopsy as a diagnostic tool.

Findings

ATTRv-F64S fibrils have a conserved fold seen in other ATTR fibrils.

Mass spectrometry identified post-translational modifications in the fibrils.

Structural consistency across tissues supports skin biopsy as a diagnostic method.

Abstract

Amyloid transthyretin-derived (ATTR) amyloidosis is a degenerative, systemic disease characterized by transthyretin fibril deposition in organs like the heart, kidneys, liver, and skin. In this study, we report the cryo-EM structure of transthyretin fibrils isolated from skin tissue of a living patient carrying a rare genetic mutation (ATTRv F64S). The structure adopts a highly conserved fold previously observed in other ATTR fibrils from various tissues or different genetic variants. Mass spectrometry was used to evaluate fibril content and to identify common post-translational modifications. The structural consistency between ATTR filaments from different tissues or patients validates non-invasive skin biopsy as a diagnostic tool.

The structure of transthyretin fibrils from skin of a living patient with a rare F64S mutation is determined. This structure reveals a conserved fold observed in other genetic variants and tissues, supporting skin biopsy as a non-invasive diagnostic tool.

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