Is Hereditary Transthyretin Amyloidosis the Third Leading Cause of Monogenic Chronic Kidney Disease, Only Behind ADPKD and Alport Disease?

Allinovi, Marco; Bergesio, Franco; Cappelli, Francesco; Chiappini, Maria Grazia; Santostefano, Marisa; Argirò, Alessia; Catalucci, Tullio; Parise, Alberto; Zampieri, Mattia; Perfetto, Federico

doi:10.1159/000526955

Cited by 2 publications

(1 citation statement)

References 15 publications

(17 reference statements)

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“…Contrary, the kidney is rarely affected in ATTR amyloidosis patients (Adams et al, 2021). When it occurs, renal malfunction is caused by cardiorenal syndrome or by direct damage caused by amyloid deposition in the glomeruli, arterioles, and medium vessels (Allinovi et al, 2022; Fenoglio et al, 2022; Lobato et al, 1998). Various mutations have been linked to renal abnormalities, yet the ATTRv-T60A variant has not been specifically addressed (Lobato & Rocha, 2012).…”

Section: Discussionmentioning

confidence: 99%

Multi-organ structural homogeneity of amyloid fibrils in ATTRv-T60A amyloidosis patients, revealed by Cryo-EM

Fernandez-Ramirez,

Nguyen,

Singh

et al. 2024

Preprint

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ATTR amyloidosis is a degenerative disorder characterized by the systemic deposition of the protein transthyretin. These amyloid aggregates of transthyretin (ATTR) can deposit in different parts of the body causing diverse clinical manifestations. Our laboratory aims to investigate a potential relationship between the different genotypes, organ of deposition, clinical phenotypes, and the structure of ATTR fibrils. Using cryo-electron microscopy, we have recently described how the neuropathic related mutations ATTRv-I84S and ATTRv-V122Δ can drive structural polymorphism in ex vivo fibrils. Here we question whether the mutation ATTRv-T60A, that commonly triggers cardiac and neuropathic symptoms, has a similar effect. To address this question, we extracted and determined the structure of ATTR-T60A fibrils from multiple organs (heart, thyroid, kidney, and liver) from the same patient and from the heart of two additional patients. We have found a consistent conformation among all the fibril structures, acquiring the closed-gate morphology previously found in ATTRwt and others ATTRv related to cardiac or mixed manifestations. The closed-gate morphology is composed by two segments of the protein that interact together forming a polar channel, where the residues glycine 57 to isoleucine 68 act as a gate of the polar cavity. Our study indicates that ATTR-T60A fibrils present in peripheral organs adopt the same structural conformation in all patients, regardless of the organ of deposition.

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Section: Discussionmentioning

confidence: 99%

Multi-organ structural homogeneity of amyloid fibrils in ATTRv-T60A amyloidosis patients, revealed by Cryo-EM

Fernandez-Ramirez,

Nguyen,

Singh

et al. 2024

Preprint

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Kidney Amyloidosis: Updates on Pathogenesis and Therapeutic Frontiers

Cervantes,

Atta

2024

Am J Nephrol

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Background: Amyloidosis includes a diverse group of rare diseases characterized by the misfolding of native or mutant proteins, leading to extracellular accumulation in various organs. While 42 proteins have been identified to date, their distribution differs between systemic and localized forms. Summary: Mass spectrometry analysis of tissue samples in the US show immunoglobulin light chain (AL) amyloidosis as the most prevalent systemic type, followed by transthyretin (ATTR). Heart and kidney involvement are common. Although there are 14 recognized types of kidney-related amyloidosis, clinicopathologic studies in the US have identified 11 types, with AL amyloidosis being the most prevalent cause of kidney involvement.

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Is Hereditary Transthyretin Amyloidosis the Third Leading Cause of Monogenic Chronic Kidney Disease, Only Behind ADPKD and Alport Disease?

Cited by 2 publications

References 15 publications

Multi-organ structural homogeneity of amyloid fibrils in ATTRv-T60A amyloidosis patients, revealed by Cryo-EM

Multi-organ structural homogeneity of amyloid fibrils in ATTRv-T60A amyloidosis patients, revealed by Cryo-EM

Kidney Amyloidosis: Updates on Pathogenesis and Therapeutic Frontiers

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