{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T22:51:20Z","timestamp":1778799080586,"version":"3.51.4"},"reference-count":54,"publisher":"S. Karger AG","issue":"4","license":[{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,1,1]],"date-time":"2024-01-01T00:00:00Z","timestamp":1704067200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiology"],"published-print":{"date-parts":[[2024]]},"abstract":"<jats:p>&lt;b&gt;&lt;i&gt;Introduction:&lt;\/i&gt;&lt;\/b&gt; Amyloidosis caused by TTR mutations (ATTRv) is a rare inherited and autosomal dominant disease. More than 150 mutants of TTR have been reported, whereas some of them remain to be investigated. &lt;b&gt;&lt;i&gt;Methods:&lt;\/i&gt;&lt;\/b&gt; A 52-year-old male presented with heart failure and clinically diagnosed ATTR cardiac amyloidosis (ATTR-CA) was recruited. Whole-exome sequencing (WES) was performed. Biochemical and biophysical experiments characterized protein stability using urea-mediated tryptophan fluorescence. Drug response was analyzed by fibril formation assay. Finally, tetramer TTR concentration in patient\u2019s serum sample was measured by ultra-performance liquid chromatography (UPLC). &lt;b&gt;&lt;i&gt;Results:&lt;\/i&gt;&lt;\/b&gt; For the proband, WES revealed a mutation (c.200G&amp;gt;T; &lt;i&gt;p.Gly67Val&lt;\/i&gt; and referred to as G47V) in TTR gene. Biochemical and biophysical kinetics study showed that the thermodynamic stability of G47V-TTR (C&lt;sub&gt;m&lt;\/sub&gt; = 2.4 &lt;sc&gt;m&lt;\/sc&gt;) was significantly lower than that of WT-TTR (C&lt;sub&gt;m&lt;\/sub&gt; = 3.4 &lt;sc&gt;m&lt;\/sc&gt;) and comparable to that of L55P-TTR (C&lt;sub&gt;m&lt;\/sub&gt; = 2.3 &lt;sc&gt;m&lt;\/sc&gt;), an early age-of-onset mutation. G47V:WT-TTR heterozygous tetramer kinetic stability (t&lt;sub&gt;1\/2&lt;\/sub&gt; = 1.4 h) was further compromised compared to that of the homozygous G47V-TTR (t&lt;sub&gt;1\/2&lt;\/sub&gt; = 3.1 h). Among three small molecule stabilizers, AG10 exhibited the best inhibition of the fibrillation of G47V-TTR homozygous protein. Using a UPLC assay, nearly 40% of TTR in this patient was calculated to be non-tetrameric. &lt;b&gt;&lt;i&gt;Conclusion:&lt;\/i&gt;&lt;\/b&gt; In this work, we reported a patient presented early onset of clinically typical ATTR-CA due to G47V-TTR mutation. Our work for the first time not only characterized the biochemical properties of G47V-TTR mutation, but also provided hints for the pathogenicity of this mutation. <\/jats:p>","DOI":"10.1159\/000538081","type":"journal-article","created":{"date-parts":[[2024,3,4]],"date-time":"2024-03-04T22:00:30Z","timestamp":1709589630000},"page":"383-395","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of Transthyretin Mutation G47V Associated with Hereditary Cardiac 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