{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T19:34:58Z","timestamp":1760729698282},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,6,9]],"date-time":"2005-06-09T00:00:00Z","timestamp":1118275200000},"content-version":"vor","delay-in-days":6583,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1987,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In a Portuguese\u2010American family with hereditary amyloid neuropathy (familial amyloidotic polyneuropathy), onset was in the seventh decade in <jats:italic>all<\/jats:italic> affected relatives. Another unusual characteristic was their origin from the Portuguese island of Madeira. In spite of this, the mutant transthyretin (TTR<jats:sup>Met30<\/jats:sup>) (the same variant prealbumin that is the circulating precursor of AF<jats:sub>P<\/jats:sub> protein in the classic Portuguese patients) could be found in the propositus plasma. In addition, three other <jats:italic>asymptomatic<\/jats:italic> relatives (ages 90, 73, and 48) were shown to carry the mutation.<\/jats:p><jats:p>Late onset and incomplete penetrance, at a clinical level, raise problems for presymptomatic detection of mutant TTR, as these tend to cluster in families. When counseling asymptomatic heterozygotes, we must consider intra\u2010familial correlation in age\u2010of\u2010onset, and the distribution of age\u2010of\u2010onset including age of unaffected heterozygotes.<\/jats:p><jats:p>This family poses interesting questions regarding pathogenesis of this degenerative process and the influence of other genetic factors, such as modifiers, epistasis, and polymorphism of the TTR genes or their regulators. A cis\u2010effect of a gene linked to the mutant gene, decreasing the synthesis of the mutant TTR and keeping a sufficient amount of the normal one in circulation, or producing some cofactor for TTR, could also explain late onset and apparently incomplete penetrance; the occasional finding of classic forms in these families would be the result of recombinatory events.<\/jats:p>","DOI":"10.1002\/ajmg.1320270213","type":"journal-article","created":{"date-parts":[[2005,6,12]],"date-time":"2005-06-12T02:52:19Z","timestamp":1118544739000},"page":"345-357","source":"Crossref","is-referenced-by-count":32,"title":["Onset in the seventh decade and lack of symptoms in heterozygotes for the TTR<sup>Met30<\/sup> mutation in hereditary amyloid neuropathy\u2014type I (Portuguese, Andrade)"],"prefix":"10.1002","volume":"27","author":[{"given":"Jorge","family":"Sequeiros","sequence":"first","affiliation":[]},{"given":"Maria Jo\u00e3o Mascarenhas","family":"Saraiva","sequence":"additional","affiliation":[]},{"given":"John M.","family":"Opitz","sequence":"additional","affiliation":[]},{"given":"James F.","family":"Reynolds","sequence":"additional","affiliation":[]}],"member":"311","published-online":{"date-parts":[[2005,6,9]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"1","article-title":"Familial amyloidosis with polyneuropathy","volume":"590","author":"Andersson R","year":"1976","journal-title":"Acta Med Scand (Suppl)"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/75.3.408"},{"key":"e_1_2_1_4_1","first-page":"119","volume-title":"Handbook of Clinical Neurology","author":"Andrade C","year":"1975"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780130622"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00287080"},{"key":"e_1_2_1_7_1","first-page":"99","volume-title":"Amyloid and Amyloidosis","author":"Bastos Lima A","year":"1980"},{"key":"e_1_2_1_8_1","first-page":"329","article-title":"Paramyloidose der peripheren Nerven in Portugal","volume":"37","author":"Becker PE","year":"1964","journal-title":"Z Menschl Vererb \u2010u Konstit Lehre"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110114"},{"key":"e_1_2_1_10_1","first-page":"590A","article-title":"Identification of a new amino acid substitution in plasma prealbumin associated with hereditary amyloidosis","volume":"33","author":"Benson MD","year":"1985","journal-title":"Clin Res"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-80079-4.50048-X"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/99.1.1"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.9.4499"},{"key":"e_1_2_1_14_1","first-page":"88","volume-title":"Amyloid and Amyloidosis","author":"Coutinho P","year":"1980"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(83)90831-8"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(62)90230-9"},{"key":"e_1_2_1_17_1","first-page":"33","article-title":"Amyloidotic polyneuropathy in a Jewish family. 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