{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,11]],"date-time":"2026-01-11T00:58:51Z","timestamp":1768093131310,"version":"3.49.0"},"reference-count":55,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:00:00Z","timestamp":1676073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","award":["59354385"],"award-info":[{"award-number":["59354385"]}],"id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Amyloidosis due to the transthyretin Ser77Tyr mutation (ATTRS77Y) is a rare autosomal\u2010dominant disorder, characterized by carpal\u2010tunnel syndrome, poly\u2010 and autonomic\u2010neuropathy, and cardiomyopathy. However, related symptoms and signs are often nonspecific and confirmatory tests are required. We describe the age and frequency of early symptoms and diagnostic features among individuals of Jewish Yemenite descent in Israel.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Records of mutation carriers were retrospectively reviewed. ATTRS77Y diagnosis was defined by the presence of amyloid in tissue and\/or amyloid\u2010related cardiomyopathy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified the Ser77Tyr mutation at the heterozygous state in 19 amyloidosis patients (mean\u00a0age at diagnosis: 62\u2009\u00b1\u20095.7\u2009years, range 49\u201370) and 30 amyloid\u2010negative carriers. The probability for disease diagnosis increased from 4.4% at age 49 to 100% at 70 and occurred earlier in males. Initial symptoms preceded diagnosis by 5\u2009\u00b1\u20093.8\u2009years (range 0\u201312) and were commonly sensory changes in the extremities. Erectile dysfunction predated these in 8\/13 (62%) males. In two patients cardiac preceded neurological symptoms. Two patients declined symptoms. Electrophysiological studies near\u00a0the\u00a0time\u00a0of diagnosis indicated a median neuropathy at the wrist in 18\/19 (95%) and polyneuropathy in 13\/19 (68%). Skin biopsy revealed epidermal denervation in 15\/16 (94%) patients. Cardiomyopathy was identified in 16\/19 (84%). Sensory complaints or epidermal denervations were present in 17\/30 (57%) of amyloid\u2010negative carriers and co\u2010occurred in 10\/30 (33%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>ATTRS77Y symptoms commonly occur after age 50, but may begin earlier. Median neuropathy, skin denervation and cardiomyopathy are frequently identified. Symptoms may be absent in patients and common in amyloid\u2010negative carriers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51741","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T12:14:34Z","timestamp":1676117674000},"page":"553-567","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>Ser77Tyr<\/scp> transthyretin amyloidosis in Israel: Initial manifestations and diagnostic features"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4633-1481","authenticated-orcid":false,"given":"Amir","family":"Dori","sequence":"first","affiliation":[{"name":"Department of Neurology Sheba Medical Center  Tel Hashomer Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Arad","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Leviev Heart Center, Sheba Medical Center  Tel Hashomer Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yishay","family":"Wasserstrum","sequence":"additional","affiliation":[{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv Israel"},{"name":"The Leviev Heart Center, Sheba Medical Center  Tel Hashomer Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur","family":"Pollak","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Hadassah Medical Center Hebrew University of Jerusalem  Jerusalem Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Nikitin","sequence":"additional","affiliation":[{"name":"Department of Neurology Sheba Medical Center  Tel Hashomer Israel"},{"name":"Sackler Faculty of Medicine Tel Aviv University  Tel Aviv 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