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Kruscal-Wallis analysis among ancestral groups. For each ancestral group the synthesis of the TTR expression scores, in terms of median, minimum and maximum, for each tissue involved in TTR amyloidosis is reported. (PDF 124 kb)

Kruscal-Wallis analysis within the American ancestral group. For each population the synthesis of the TTR expression scores, in terms of median, minimum and maximum, for each tissue involved in TTR amyloidosis is reported. Detailed information about population definitions is available at http://www.1000genomes.org/about . (PDF 115 kb)

Kruscal-Wallis analysis within the Eastern Asian ancestral group. For each population the synthesis of the TTR expression scores, in terms of median, minimum and maximum, for each tissue involved in TTR amyloidosis is reported. Detailed information about population definitions is available at http://www.1000genomes.org/about . (PDF 101 kb)

Kruscal-Wallis analysis within the European ancestral group. For each population the synthesis of the TTR expression scores, in terms of median, minimum and maximum, for each tissue involved in TTR amyloidosis is reported. Detailed information about population definitions is available at http://www.1000genomes.org/about . (PDF 102 kb)

A) Clumped datasets for the African ancestry. Colors refer to variants in the LD blocks (r2 > 0.5; different colors represent different LD blocks) and X = presence of a variant in a specific dataset after the LD clumping analysis. B) Clumped datasets for the European ancestry. Color refer to variants in the LD block (r2 > 0.5; different colors represent different LD blocks) and X = presence of a variant in a specific dataset after the LD clumping analysis. C) Clumped datasets for the Eastern Asian ancestry. Colors refer to variants in the LD blocks (r2 > 0.5; different colors represent different LD blocks) and X = presence of a variant in a specific dataset after the LD clumping analysis D) Clumped datasets for the Southern Asian ancestry. Colors refer to variants in the LD blocks (r2 > 0.5; different colors represent different LD blocks) and X = presence of a variant in a specific dataset after the LD clumping analysis. E) Clumped datasets for the American ancestry. Colors refer to variants in the LD blocks (r2 > 0.5; different colors represent different LD blocks) and X = presence of a variant in a specific dataset after the LD clumping analysis. (PDF 88 kb)

Kruscal-Wallis analysis within the Southern Asian ancestral group. For each population the synthesis of the TTR expression scores, in terms of median, minimum and maximum, for each tissue involved in TTR amyloidosis is reported. Detailed information about population definitions is available at http://www.1000genomes.org/about . (PDF 101 kb)

Heatmap of the Dunnâ s post-hoc test among the ancestral groups. The colors refer to different significance levels. Detailed information about population definitions is available at http://www.1000genomes.org/about (AFR: Africa, EUR: Europe, EAS: East Asia, SAS: South Asia, AMR: America). (PDF 201 kb)

Inter-ethnic clinical diversity associated with TTR mutations. Each mutation is named in accordance of the missense substitution in the mature protein. For each mutation, rsID and protein change in the protein precursor is also reported. (PDF 137 kb)

Kruscal-Wallis analysis within the African ancestral group. For each population the synthesis of the TTR expression scores, in terms of median, minimum and maximum, for each tissue involved in TTR amyloidosis is reported. Detailed information about population definitions is available at http://www.1000genomes.org/about . (PDF 90 kb)

Hereditary transthyretin (TTR) amyloidosis (ATTRv) is a dominantly inherited, adult-onset, progressive, and fatal disease caused by mutations in the transthyretin gene. Therapeutic agents approved for this disease include the TTR stabilizer tafamidis and the gene-silencing drugs patisiran and inotersen. Inotersen is an antisense oligonucleotide that suppresses the hepatic production of transthyretin. After European Medical Agency approval in 2018, an early-access program was opened in Italy, and in this article, we present the long-term outcome of a cohort of Italian ATTRv patients who received inotersen within this program.This is a multicenter, observational, retrospective study of patients affected by ATTRv that started inotersen during the early-access program. The primary end point was safety. Secondary end points included change from baseline in familial amyloid polyneuropathy (FAP) stage, Polyneuropathy Disability, Neuropathy Impairment Scale, Compound Autonomic Dysfunction Test, Norfolk Quality of Life-Diabetic Neuropathy, troponin, N-terminal pro-brain natriuretic peptide, interventricular septum thickness, and body mass index.In total, 23 patients were enrolled. No patient permanently discontinued the treatment because of thrombocytopenia, and no cases of severe thrombocytopenia were observed. Five patients discontinued the treatment permanently because of voluntary withdrawal (two patients), renal failure after infective pyelonephritis, not related to inotersen, drug-related hypotension, and amyloid-negative crescentic glomerulonephritis. In seven patients, dosing frequency was reduced to every 2 weeks due to recurrent thrombocytopenia. Considering the FAP stage, only two patients worsened, whereas the other 21 patients remained stable until the last follow-up available.The long-term safety profile of inotersen is favorable. Neurologic disease severity at baseline is the main factor associated with progression.