{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T09:06:54Z","timestamp":1793783214386,"version":"4.6.1"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["74310325"],"award-info":[{"award-number":["74310325"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Nanfang Hospital Baiyun Branch Dean\u2019s Fund","award":["BYYZ24007"],"award-info":[{"award-number":["BYYZ24007"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Our study aimed to report the clinical features and epidemiological characteristics of hereditary transthyretin amyloidosis-polyneuropathy(ATTRv-PN) with\n                      <jats:italic>TTR<\/jats:italic>\n                      Ala97Ser(p.Ala117Ser) mutation from South Mainland China.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We identified 21 patients from 20 families diagnosed with Ala97Ser ATTRv-PN based on strict clinical and electrophysiological criteria from three centers. Clinical and laboratory data were retrospectively retrieved for analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A gender imbalance was noted with a male-to-female ratio of 18:3. All patients showed late onset, with the age of onset at 56.5\u2009\u00b1\u20097.2 years. The predominant initial symptom, reported by 15 patients (71.4%), was numbness. Paraesthesia was present in all patients. Eighteen patients (85.7%) had autonomic dysfunction. Cardiac, renal, and ocular dysfunctions were noted in 17 (80.9%), 4(19.0%), and 4(19.0%) patients, respectively. Nerve conduction studies have shown axonal-type sensorimotor polyneuropathy. The decline in sensory nerve action potentials was more noticeable than in compound muscle action potentials. The nerve damage present in the lower limbs was more severe than that in the upper limbs. Nerve biopsy revealed positive Congo red staining in 11\/15 patients (73.3%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>ATTRv-PN appears relatively rare in South Mainland China, with our study providing the largest cohort of Ala97Ser mutation cases to date. We found a significant founder effect by combining the clinical and demographic characteristics. That helps us understand the gene\u2019s transmission pathway and lays the foundation for carrier screening and tertiary prevention and control. We also propose a new scoring model and demonstrate that this model allows the profiling of different genotypes of ATTRv-PN, facilitating early clinical detection and diagnosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-03733-0","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T07:29:11Z","timestamp":1745825351000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Clinical features of hereditary transthyretin amyloidosis-polyneuropathy with transthyretin Ala97Ser(p.Ala117Ser) mutation in South Mainland China"],"prefix":"10.1186","volume":"20","author":[{"given":"Yeli","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingxian","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiying","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingchao","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruxu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7388-8659","authenticated-orcid":false,"given":"Haishan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"issue":"7","key":"3733_CR1","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1038\/s41582-019-0210-4","volume":"15","author":"D Adams","year":"2019","unstructured":"Adams D, Koike H, Slama M, et al. Hereditary transthyretin amyloidosis: a model of medical progress for a fatal disease [J]. Nat Reviews Neurol. 2019;15(7):387\u2013404.","journal-title":"Nat Reviews Neurol"},{"issue":"3","key":"3733_CR2","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1093\/brain\/75.3.408","volume":"75","author":"C Andrade","year":"1952","unstructured":"Andrade C. A peculiar form of peripheral neuropathy; familiar atypical generalized amyloidosis with special involvement of the peripheral nerves [J]. Brain. 1952;75(3):408\u201327.","journal-title":"Brain"},{"issue":"6","key":"3733_CR3","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1001\/archneur.1968.00470360015001","volume":"18","author":"S Araki","year":"1968","unstructured":"Araki S, Mawatari S, Ohta M, et al. Polyneuritic amyloidosis in a Japanese family [J]. Arch Neurol. 1968;18(6):593\u2013602.","journal-title":"Arch Neurol"},{"key":"3733_CR4","first-page":"1","volume":"590","author":"R Andersson","year":"1976","unstructured":"Andersson R. Familial amyloidosis with polyneuropathy. A clinical study based on patients living in Northern Sweden [J]. Acta Med Scand Suppl. 1976;590:1\u201364.","journal-title":"Acta Med Scand Suppl"},{"issue":"1","key":"3733_CR5","first-page":"62","volume":"12","author":"JK Ryu","year":"2005","unstructured":"Ryu JK, Baik HW, Bae JS, et al. Familial amyloid polyneuropathy in Korea: the first case report with a proven ATTR Lys35Asn gene [J]. Amyloid: Int J Experimental Clin Invest: Official J Int Soc Amyloidosis. 2005;12(1):62\u20134.","journal-title":"Amyloid: Int J Experimental Clin Invest: Official J Int Soc Amyloidosis"},{"issue":"4","key":"3733_CR6","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1111\/cge.12500","volume":"88","author":"DB Zhen","year":"2015","unstructured":"Zhen DB, Swiecicki PL, Zeldenrust SR, et al. Frequencies and geographic distributions of genetic mutations in transthyretin- and non-transthyretin-related Familial amyloidosis [J]. Clin Genet. 2015;88(4):396\u2013400.","journal-title":"Clin Genet"},{"issue":"1","key":"3733_CR7","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1111\/jns.12196","volume":"22","author":"G Liu","year":"2017","unstructured":"Liu G, Ni W, Wang H, et al. Clinical features of Familial amyloid polyneuropathy carrying transthyretin mutations in four Chinese kindreds [J]. J Peripheral Nerv System: JPNS. 2017;22(1):19\u201326.","journal-title":"J Peripheral Nerv System: JPNS"},{"issue":"1","key":"3733_CR8","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1186\/s12883-021-02243-3","volume":"21","author":"N Pasutharnchat","year":"2021","unstructured":"Pasutharnchat N, Taychargumpoo C, Vorasettakarnkij Y, et al. Ala97Ser transthyretin amyloidosis-associated polyneuropathy, clinical and neurophysiological profiles in a Thai cohort [J]. BMC Neurol. 2021;21(1):206.","journal-title":"BMC Neurol"},{"issue":"Suppl 1","key":"3733_CR9","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1097\/WCO.0000000000000288","volume":"29","author":"Y Parman","year":"2016","unstructured":"Parman Y, Adams D, Obici L, et al. Sixty years of transthyretin Familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP [J]. Curr Opin Neurol. 2016;29(Suppl 1):S3\u201313.","journal-title":"Curr Opin Neurol"},{"issue":"4","key":"3733_CR10","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/mus.20821","volume":"36","author":"MD Benson","year":"2007","unstructured":"Benson MD, Kincaid JC. The molecular biology and clinical features of amyloid neuropathy [J]. Muscle Nerve. 2007;36(4):411\u201323.","journal-title":"Muscle Nerve"},{"key":"3733_CR11","doi-asserted-by":"crossref","unstructured":"Saraiva MJ, Birken S, Costa PP, et al. Family studies of the genetic abnormality in transthyretin (prealbumin) in Portuguese patients with Familial amyloidotic polyneuropathy [J]. Volume 435. Annals of the New York Academy of Sciences; 1984. pp. 86\u2013100.","DOI":"10.1111\/j.1749-6632.1984.tb13742.x"},{"key":"3733_CR12","doi-asserted-by":"crossref","unstructured":"Liu YT, Lee YC, Yang CC et al. Transthyretin Ala97Ser in Chinese-Taiwanese patients with familial amyloid polyneuropathy: genetic studies and phenotype expression [J]. J Neurol Sci. 2008;267(1\u20132):91\u20139.","DOI":"10.1016\/j.jns.2007.10.011"},{"issue":"6","key":"3733_CR13","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1212\/WNL.0b013e3181ec7fda","volume":"75","author":"NC Yang","year":"2010","unstructured":"Yang NC, Lee MJ, Chao CC, et al. Clinical presentations and skin denervation in amyloid neuropathy due to transthyretin Ala97Ser [J]. Neurology. 2010;75(6):532\u20138.","journal-title":"Neurology"},{"issue":"2","key":"3733_CR14","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1002\/ana.24438","volume":"78","author":"CC Chao","year":"2015","unstructured":"Chao CC, Huang CM, Chiang HH, et al. Sudomotor innervation in transthyretin amyloid neuropathy: pathology and functional correlates [J]. Ann Neurol. 2015;78(2):272\u201383.","journal-title":"Ann Neurol"},{"issue":"1","key":"3733_CR15","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1186\/s12883-017-0957-4","volume":"17","author":"HC Hsu","year":"2017","unstructured":"Hsu HC, Liao MF, Hsu JL, et al. Phenotypic expressions of hereditary transthyretin Ala97Ser related amyloidosis (ATTR) in Taiwanese [J]. BMC Neurol. 2017;17(1):178.","journal-title":"BMC Neurol"},{"key":"3733_CR16","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1016\/j.jocn.2018.10.040","volume":"60","author":"Z Yuan","year":"2019","unstructured":"Yuan Z, Guo L, Liu X, et al. Familial amyloid polyneuropathy with chronic paroxysmal dry cough in Mainland China: A Chinese family with a proven heterozygous missense mutation c.349G\u2009>\u2009T in the transthyretin gene [J]. J Clin Neuroscience: Official J Neurosurgical Soc Australasia. 2019;60:164\u20136.","journal-title":"J Clin Neuroscience: Official J Neurosurgical Soc Australasia"},{"issue":"1","key":"3733_CR17","first-page":"7","volume":"48","author":"HZ Guan","year":"2015","unstructured":"Guan HZ, Liu Q, Chen L, Qian M, Liu Z, Guan YZ, Ren HT, Zhao YH, Chen M, Tian Z, Zou X, Cui LY. The clinical, pathological and genetic studies of transthyretin Familial amyloid polyneuropathy. Chin J Neurol. 2015;48(1):7\u201312.","journal-title":"Chin J Neurol"},{"issue":"5","key":"3733_CR18","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1002\/mus.26034","volume":"57","author":"HH Schmidt","year":"2018","unstructured":"Schmidt HH, Waddington-Cruz M, Botteman MF, et al. Estimating the global prevalence of transthyretin Familial amyloid polyneuropathy [J]. Muscle Nerve. 2018;57(5):829\u201337.","journal-title":"Muscle Nerve"},{"key":"3733_CR19","doi-asserted-by":"crossref","unstructured":"Liu JY, Guo YJ, Zhou CK et al. Clinical and histopathological features of familial amyloidotic polyneuropathy with transthyretin Val30Ala in a Chinese family [J]. J Neurol Sci. 2011;304(1\u20132):83\u20136.","DOI":"10.1016\/j.jns.2011.02.005"},{"issue":"21","key":"3733_CR20","doi-asserted-by":"publisher","first-page":"2902","DOI":"10.4103\/0366-6999.168048","volume":"128","author":"LC Meng","year":"2015","unstructured":"Meng LC, Lyu H, Zhang W, et al. Hereditary transthyretin amyloidosis in eight Chinese families [J]. Chin Med J. 2015;128(21):2902\u20135.","journal-title":"Chin Med J"},{"key":"3733_CR21","doi-asserted-by":"crossref","unstructured":"Chen H, Zhou X, Wang J et al. Exome Sequencing and Gene Prioritization Correct Misdiagnosis in a Chinese Kindred with Familial Amyloid Polyneuropathy [J]. Scientific reports. 2016;6(26362).","DOI":"10.1038\/srep26362"},{"issue":"4","key":"3733_CR22","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1002\/acn3.51328","volume":"8","author":"K Du","year":"2021","unstructured":"Du K, Li F, Wang H, et al. Hereditary transthyretin amyloidosis in Mainland China: a unicentric retrospective study [J]. Ann Clin Transl Neurol. 2021;8(4):831\u201341.","journal-title":"Ann Clin Transl Neurol"},{"issue":"5","key":"3733_CR23","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1002\/acn3.778","volume":"6","author":"HC Chao","year":"2019","unstructured":"Chao HC, Liao YC, Liu YT, et al. Clinical and genetic profiles of hereditary transthyretin amyloidosis in Taiwan [J]. Ann Clin Transl Neurol. 2019;6(5):913\u201322.","journal-title":"Ann Clin Transl Neurol"},{"key":"3733_CR24","doi-asserted-by":"crossref","unstructured":"Misu K, Hattori N, Nagamatsu M et al. Late-onset Familial amyloid polyneuropathy type I (transthyretin Met30-associated Familial amyloid polyneuropathy) unrelated to endemic focus in Japan. Clinicopathological and genetic features [J]. Brain, 1999, 122 (Pt 10)(1951-62.","DOI":"10.1093\/brain\/122.10.1951"},{"issue":"3","key":"3733_CR25","doi-asserted-by":"publisher","first-page":"826","DOI":"10.1111\/ene.15176","volume":"29","author":"J Castro","year":"2022","unstructured":"Castro J, Miranda B, de Castro I, et al. Changes in nerve conduction studies predate clinical symptoms onset in early onset Val30Met hereditary ATTR amyloidosis [J]. Eur J Neurol. 2022;29(3):826\u201332.","journal-title":"Eur J Neurol"},{"issue":"2","key":"3733_CR26","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1111\/jon.12956","volume":"32","author":"K Du","year":"2022","unstructured":"Du K, Xu K, Chu X, et al. Vagus nerve ultrasound in transthyretin Familial amyloid polyneuropathy: A pilot study [J]. J Neuroimaging: Official J Am Soc Neuroimaging. 2022;32(2):285\u201391.","journal-title":"J Neuroimaging: Official J Am Soc Neuroimaging"},{"key":"3733_CR27","doi-asserted-by":"crossref","unstructured":"Luigetti M, Di Paolantonio A, Guglielmino V, et al. Neurol sciences: official J Italian Neurol Soc Italian Soc Clin Neurophysiol. 2022;43(4):2845\u20138. Neurofilament light chain as a disease severity biomarker in ATTRv: data from a single-centre experience [J].","DOI":"10.1007\/s10072-021-05850-7"},{"issue":"5","key":"3733_CR28","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1111\/ene.15268","volume":"29","author":"L Leonardi","year":"2022","unstructured":"Leonardi L, Adam C, Beaudonnet G, et al. Skin amyloid deposits and nerve fiber loss as markers of neuropathy onset and progression in hereditary transthyretin amyloidosis [J]. Eur J Neurol. 2022;29(5):1477\u201387.","journal-title":"Eur J Neurol"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-03733-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-03733-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-03733-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T07:29:14Z","timestamp":1745825354000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-025-03733-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["3733"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-03733-0","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-5950252\/v1","asserted-by":"object"}]},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]},"assertion":[{"value":"3 February 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 April 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 April 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare that there is no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Approved by Medical Ethics Committee of Southern Medical University Southern Hospital.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"A previous version of this manuscript has been published as a preprint on Research Square (DOI:\n                      \n                      , available at\n                      \n                      .","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Preprint disclosure"}}],"article-number":"202"}}