{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:42:32Z","timestamp":1790206952975,"version":"4.1.0"},"reference-count":38,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2005,6,3]],"date-time":"2005-06-03T00:00:00Z","timestamp":1117756800000},"content-version":"vor","delay-in-days":5102,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1991,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We report identification, biochemical, clinical, and genetic studies of an apparently benign, electrophoretic variant of serum prealbumin (PALB, transthyretin, TTR) in a North American kindred of Swedish ancestry. The variant polypeptide stems from a C to T point mutation in exon 4 which results in methionine instead of threonine at position 119 of the mature molecule. It was discovered incidentally in a girl with classic alpha\u20101\u2010antitrypsin (A1AT) deficiency and her father during diagnostic A1AT phenotyping by ISO\u2010DALT high\u2010resolution two\u2010dimensional electrophoresis (2DE). Twelve relatives in the four\u2010generation paternal kindred, including five individuals who were heterozygous for the variant prealbumin, were studied. In each of these five heterozygotes, the variant allele product was equimolar and isoelectric with the normal protein, yet migrated with an apparently lower mass in the SDS\u2010PAGE dimension. The inheritance pattern was consistent with autosomal dominant transmission. Histories and physical examinations showed no evidence of amyloidosis, as has been observed with other variants of prealbumin. Mean values of serum prealbumin and retinol binding protein levels were higher in the carriers as compared to the normal relatives in the family, but the difference was not statistically significant. Thyroid hormone levels and distribution of thyroxine and triiodothyronine among binding proteins in serum were within reference limits. Four members of the lineage had dominant, scalp\u2010restricted keratinaceous cysts, yet only three of these four individuals had the variant. We counseled the family that this is likely a benign variant with regard to amyloidosis\u2010related morbidity or shortened life span, although senile effects cannot be entirely ruled out. The provisional designation assigned to this allele is PALB<jats:sup>CHICAGO<\/jats:sup>. The substitution of methionine at position 119, as predicted by the DNA sequence, was confirmed by amino acid sequencing of CNBr and tryptic peptides. This substitution occurs at a CpG dinucleotide that may be a point mutational \u201chot spot,\u201d as has been postulated for the methionine\u201030 and isoleucine\u2010122 PALB variants. The apparently lower mass of the variant probably results from a more compact conformation in SDS. With the exception of histidine\u201058, a charge substitution, all other amyloidosis\u2010related prealbumin variant polypeptides had normal mobility in the ISODALT 2DE system.<\/jats:p>","DOI":"10.1002\/ajmg.1320390415","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T13:27:42Z","timestamp":1118496462000},"page":"442-452","source":"Crossref","is-referenced-by-count":31,"title":["Biochemical and clinical characterization of prealbumin <sup>CHICAGO<\/sup>: An apparently benign variant of serum prealbumin (transthyretin) discovered with high\u2010resolution two\u2010dimensional electrophoresis"],"prefix":"10.1002","volume":"39","author":[{"given":"Harold H.","family":"Harrison","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edys D.","family":"Gordon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Merrill D.","family":"Benson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2005,6,3]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.74.12.5421"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90229-4"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90230-0"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-2697(79)80157-8"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111699"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780300210"},{"key":"e_1_2_1_8_1","first-page":"129","article-title":"Genetic amyloidosis: Recent advances","volume":"18","author":"Benson MD","year":"1989","journal-title":"Adv Nephrol"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(78)90368-6"},{"key":"e_1_2_1_10_1","first-page":"226","volume":"40","author":"Cornwell GG","year":"1987","journal-title":"Prealbumin:Its association with amyloid J Clin Pathol"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.9.4499"},{"key":"e_1_2_1_12_1","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1093\/clinchem\/30.12.1972","article-title":"Quality control and technical outcome of high resolution two\u2010dimensional electrophoresis in a clinical laboratory setting","volume":"30","author":"Daufeldt JA","year":"1984","journal-title":"Clin Chem"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(83)90831-8"},{"key":"e_1_2_1_14_1","doi-asserted-by":"crossref","first-page":"12764","DOI":"10.1016\/S0021-9258(18)45272-6","article-title":"Detection of heritable mutations in protein expression","volume":"262","author":"Giometti CS","year":"1987","journal-title":"J Biol Chem"},{"key":"e_1_2_1_15_1","first-page":"827","article-title":"Human lymphocyte polymorphisms detected by quantitative two\u2010dimensional electrophoresis","volume":"35","author":"Goldman D","year":"1983","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/elps.1150030404"},{"key":"e_1_2_1_17_1","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1093\/clinchem\/30.12.1981","article-title":"Improved record keeping and photography of silver\u2010stained two\u2010dimensional electrophoretograms by way of \u201cXRD images.\u201d","volume":"30","author":"Harrison HH","year":"1984","journal-title":"Clin Chem"},{"key":"e_1_2_1_18_1","first-page":"1083","article-title":"Clinical applications of high resolution two\u2010dimensional electrophoresis (2DE) of proteins: Comparative analysis by 2DE of proteins in high resolution agarose electrophoresis (HRE) bands and current medical indications for 2DE analysis of serum proteins","volume":"35","author":"Harrison HH","year":"1989","journal-title":"Clin Chem"},{"key":"e_1_2_1_19_1","first-page":"202","article-title":"Typing of genetic variants of alpha\u20101\u2010antitrypsin by electrofocusing. 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