{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T06:15:09Z","timestamp":1771481709759,"version":"3.50.1"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:00:00Z","timestamp":1771459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a progressive multisystem disorder caused by pathogenic\n                      <jats:italic>TTR<\/jats:italic>\n                      variants. Aim of this study is to delineate the clinical and genetic feature of ATTRv-PN in China and to evaluate diagnostic strategies for earlier and accurate recognition.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated two genetically confirmed Chinese patients with ATTRv-PN through comprehensive assessments, including electrophysiology, sural nerve biopsy, autonomic testing, cardiac imaging, neuroimaging, and cerebrospinal fluid analysis. Additionally, logistic regression was performed on 70 reported p.Val50Met cases to examine the relationship between age at onset and amyloid detection in sural nerve biopsies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The two patients carried the p.Val50Met and p.Glu74Gly variants in the\n                      <jats:italic>TTR<\/jats:italic>\n                      gene, respectively. Both presented with distal paresthesia as the initial symptom and exhibited length-dependent, axonal-predominant sensorimotor polyneuropathy. Autonomic manifestations included alternating diarrhea\/constipation and post-exertional hyperhidrosis. Subclinical cardiac abnormalities were identified, encompassing elevated biomarker of early cardiac strain, valvular regurgitation, left ventricular hypertrophy, and late gadolinium enhancement. In patient 1, sural nerve pathology showed marked loss of myelinated and unmyelinated fibers with perivascular lymphocytic infiltration but no amyloid deposition. Logistic regression revealed no significant association between age at onset and biopsy amyloid positivity (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.91).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study expands the clinical and genetic landscape of ATTRv-PN in China and highlighted the heterogeneity of amyloid detection in nerve biopsies. Accurate and timely diagnosis requires an integrated approach combining clinical, electrophysiological, pathological, genetic, and multimodal imaging assessments to facilitate early initiation of disease-modifying therapies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1715134","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:23:24Z","timestamp":1771478604000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and genetic features of hereditary transthyretin amyloidosis with polyneuropathy in China: insights from case analysis and literature review"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaoyang","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Neurology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Neurology, Hebei Hospital of Xuanwu Hospital Capital Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yajun","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Minimally Invasive Spine Surgery, Hebei Hospital of Xuanwu Hospital Capital Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Neurology, Hebei Hospital of Xuanwu Hospital Capital Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Neurology, Hebei Hospital of Xuanwu Hospital Capital Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingchuan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology, The First Hospital of Hebei Medical University","place":["Shijiazhuang, Hebei, China"]},{"name":"Department of Neurology, Hebei Hospital of Xuanwu Hospital Capital Medical University","place":["Shijiazhuang, Hebei, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1056\/NEJMoa1716153","article-title":"Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis","volume":"379","author":"Adams","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2109","DOI":"10.1007\/s00415-019-09688-0","article-title":"Expert consensus recommendations to improve diagnosis of ATTR amyloidosis with polyneuropathy","volume":"268","author":"Adams","year":"2021","journal-title":"J. Neurol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1080\/13506129.2022.2043270","article-title":"Characteristics of patients with autonomic dysfunction in the transthyretin amyloidosis outcomes survey (THAOS)","volume":"29","author":"Barroso","year":"2022","journal-title":"Amyloid"},{"key":"B4","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1016\/j.nmd.2015.05.010","article-title":"Three Turkish families with different transthyretin mutations","volume":"25","author":"Bekircan-Kurt","year":"2015","journal-title":"Neuromuscul. Disord."},{"key":"B5","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1056\/NEJMoa1716793","article-title":"Inotersen treatment for patients with hereditary transthyretin amyloidosis","volume":"379","author":"Benson","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1111\/j.1529-8027.2011.00331.x","article-title":"Variable presentations of TTR-related familial amyloid polyneuropathy in seventeen patients","volume":"16","author":"Cappellari","year":"2011","journal-title":"J. Peripher Nerv. Syst."},{"key":"B7","doi-asserted-by":"publisher","first-page":"668","DOI":"10.1136\/jnnp-2021-327909","article-title":"Novel approaches to diagnosis and management of hereditary transthyretin amyloidosis","volume":"93","author":"Carroll","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1093\/brain\/awaf028","article-title":"Transthyretin variants impact blood-nerve barrier and neuroinflammation in amyloidotic neuropathy","volume":"148","author":"Chao","year":"2025","journal-title":"Brain"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1002\/ana.27203","article-title":"A multicenter study of hereditary transthyretin amyloidosis in China","volume":"97","author":"Chu","year":"2025","journal-title":"Ann. Neurol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1007\/s00415-019-09671-9","article-title":"Inotersen preserves or improves quality of life in hereditary transthyretin amyloidosis","volume":"267","author":"Coelho","year":"2020","journal-title":"J. Neurol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1080\/13506129.2022.2070470","article-title":"A natural history analysis of asymptomatic TTR gene carriers as they develop symptomatic transthyretin amyloidosis in the transthyretin amyloidosis outcomes survey (THAOS)","volume":"29","author":"Coelho","year":"2022","journal-title":"Amyloid"},{"key":"B12","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1080\/13506129.2024.2368860","article-title":"Transthyretin monomers: a new plasma biomarker for pre-symptomatic transthyretin-related amyloidosis","volume":"31","author":"Costa-Rodrigues","year":"2024","journal-title":"Amyloid"},{"key":"B13","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/acn3.51328","article-title":"Hereditary transthyretin amyloidosis in mainland China: a unicentric retrospective study","volume":"8","author":"Du","year":"2021","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"fcz032","DOI":"10.1093\/braincomms\/fcz032","article-title":"Clinicopathological correlations of sural nerve biopsies in TTR Val30Met familial amyloid polyneuropathy","volume":"1","author":"Fernandes","year":"2019","journal-title":"Brain Commun."},{"key":"B15","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1056\/NEJMoa2107454","article-title":"CRISPR-Cas9 in vivo gene editing for transthyretin amyloidosis","volume":"385","author":"Gillmore","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1080\/13506129.2020.1841623","article-title":"New data on the genetic profile and penetrance of hereditary Val30Met transthyretin amyloidosis in Sweden","volume":"28","author":"Gorram","year":"2021","journal-title":"Amyloid"},{"key":"B17","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1111\/j.1399-0004.1988.tb03434.x","article-title":"Diagnosis of familial amyloidotic polyneuropathy in Sweden by RFLP analysis","volume":"33","author":"Holmgren","year":"1988","journal-title":"Clin. Genet."},{"key":"B18","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1002\/path.2411","article-title":"Amyloid fibril composition is related to the phenotype of hereditary transthyretin V30M amyloidosis","volume":"216","author":"Ihse","year":"2008","journal-title":"J. Pathol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1212\/wnl.58.7.1001","article-title":"Familial transthyretin-type amyloid polyneuropathy in Japan: clinical and genetic heterogeneity","volume":"58","author":"Ikeda","year":"2002","journal-title":"Neurology"},{"key":"B20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3109\/13506129.2012.674580","article-title":"Late-onset familial amyloid polyneuropathy in Japan","volume":"19","author":"Koike","year":"2012","journal-title":"Amyloid"},{"key":"B21","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1212\/01.wnl.0000132966.36437.12","article-title":"Pathology of early-vs late-onset TTR Met30 familial amyloid polyneuropathy","volume":"63","author":"Koike","year":"2004","journal-title":"Neurology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"53","DOI":"10.3109\/13506129.2011.565524","article-title":"Diagnosis of sporadic transthyretin Val30Met familial amyloid polyneuropathy: a practical analysis","volume":"18","author":"Koike","year":"2011","journal-title":"Amyloid"},{"key":"B23","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.jns.2018.09.011","article-title":"The morphology of amyloid fibrils and their impact on tissue damage in hereditary transthyretin amyloidosis: an ultrastructural study","volume":"394","author":"Koike","year":"2018","journal-title":"J. Neurol. Sci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1212\/WNL.0000000000004178","article-title":"Sural nerve injury in familial amyloid polyneuropathy: MR neurography vs clinicopathologic tools","volume":"89","author":"Kollmer","year":"2017","journal-title":"Neurology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/brainsci10110780","article-title":"hATTR pathology: nerve biopsy results from Italian referral centers","volume":"10","author":"Luigetti","year":"2020","journal-title":"Brain Sci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1002\/mus.22229","article-title":"Amyloid neuropathy mimicking chronic inflammatory demyelinating polyneuropathy","volume":"45","author":"Mathis","year":"2012","journal-title":"Muscle Nerve"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1007","DOI":"10.1056\/NEJMoa1805689","article-title":"Tafamidis treatment for patients with transthyretin amyloid cardiomyopathy","volume":"379","author":"Maurer","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.4103\/0366-6999.168048","article-title":"Hereditary transthyretin amyloidosis in eight Chinese families","volume":"128","author":"Meng","year":"2015","journal-title":"Chin. Med. J. Engl."},{"key":"B29","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1093\/brain\/122.10.1951","article-title":"Late-onset familial amyloid polyneuropathy type I (transthyretin Met30-associated familial amyloid polyneuropathy) unrelated to endemic focus in Japan. Clinicopathological and genetic features","volume":"122","author":"Misu","year":"1999","journal-title":"Brain"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1016\/j.acra.2025.01.022","article-title":"Cardiac amyloidosis: a comprehensive review of imaging findings","volume":"32","author":"Mohseni","year":"2025","journal-title":"Acad. Radiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"2025","DOI":"10.1002\/ejhf.3339","article-title":"Evaluation of the 2021 ESC recommendations for family screening in hereditary transthyretin cardiac amyloidosis","volume":"26","author":"Muller","year":"2024","journal-title":"Eur. J. Heart Fail"},{"key":"B32","doi-asserted-by":"publisher","first-page":"957","DOI":"10.1007\/s11739-022-02958-2","article-title":"Circulating biomarkers in diagnosis and management of cardiac amyloidosis: a review for internist","volume":"17","author":"Perfetto","year":"2022","journal-title":"Intern Emerg. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3390\/cells12192383","article-title":"Current evidence supporting the role of immune response in ATTRv amyloidosis","volume":"12","author":"Plantone","year":"2023","journal-title":"Cells"},{"key":"B34","doi-asserted-by":"publisher","first-page":"340","DOI":"10.1007\/s00415-025-13072-6","article-title":"Elevated serum concentrations of GFAP in hereditary transthyretin amyloidosis since pre-symptomatic stages","volume":"272","author":"Plantone","year":"2025","journal-title":"J. Neurol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"787618","DOI":"10.3389\/fcvm.2022.787618","article-title":"Multimodality imaging in the evaluation and prognostication of cardiac amyloidosis","volume":"9","author":"Scheel","year":"2022","journal-title":"Front. Cardiovasc Med."},{"key":"B36","doi-asserted-by":"publisher","first-page":"e70277","DOI":"10.1111\/ene.70277","article-title":"Intracutaneous amyloid deposition is associated with nerve conduction studies deterioration in presumed asymptomatic pathogenic variant TTR carriers","volume":"32","author":"Schulz","year":"2025","journal-title":"Eur. J. Neurol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1002\/ajmg.1320600606","article-title":"Genetic epidemiology of familial amyloidotic polyneuropathy (FAP)-type I in povoa do varzim and vila do conde (north of Portugal)","volume":"60","author":"Sousa","year":"1995","journal-title":"Am. J. Med. Genet."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1914","DOI":"10.1001\/archneur.58.11.1914","article-title":"A case of familial amyloid polyneuropathy homozygous for the transthyretin Val30Met gene with motor-dominant sensorimotor polyneuropathy and unusual sural nerve pathological findings","volume":"58","author":"Yoshioka","year":"2001","journal-title":"Arch. Neurol."}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1715134\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T05:23:25Z","timestamp":1771478605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1715134\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,19]]},"references-count":38,"alternative-id":["10.3389\/fgene.2026.1715134"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1715134","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,19]]},"article-number":"1715134"}}