{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T21:38:08Z","timestamp":1781127488099,"version":"3.54.1"},"reference-count":50,"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":7124,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1985,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cystinuria is a recessively inherited transport disorder, with at least three mutant alleles (I, II, and III) demonstrable. I\/I, II\/II, and III\/III homozygotes and I\/II, I\/III, and II\/III compound heterozygotes (cystinuric patients) have high urinary concentrations of cystine, lysine, arginine, and ornithine and frequently form cystine stones. +\/I heterozygotes (nondetectable) are phenotypically normal, whereas +\/II and +\/III heterozygotes (detectable) show variable increases in urinary cystine and lysine concentration and at times increases in urinary arginine levels. The objectives of the present study were to determine the frequency of +\/II heterozygotes among stone\u2010forming and nonstone\u2010forming individuals from the same region of Brazil and to evaluate the possible relationship between heterozygous cystinuria and urinary lithiasis.<\/jats:p><jats:p>When urine samples from 5,150 individuals (5,000 nonstone\u2010forming individuals and 150 stone\u2010forming individuals) were screened by the qualitative cyanidenitroprusside cystine test, by thin\u2010layer amino acid chromatography, and by quantitative amino acid determination by ion\u2010exchange chromatography, 32 +\/II or +\/III heterozygotes (26 nonstone\u2010forming and six stone\u2010forming individuals) were detected. The frequency of detectable heterozygotes among the stone\u2010forming individuals (1:25) was significantly higher than that among nonstone\u2010forming individuals (1:104), which provides additional evidence that heterozygosity for +\/II and +\/III cystinuria is a risk factor in the formation of urinary stones. No significant difference was detected in urinary cystine concentration or in terms of the various characteristics of urolithiasis when stone\u2010forming heterozygotes were compared to nonstone\u2010forming heterozygotes. These data suggest that the tendency towards stone\u2010forming among heterozygotes is probably owing to a complex and multifactorial mechanism.<\/jats:p>","DOI":"10.1002\/ajmg.1320220407","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T20:01:11Z","timestamp":1118520071000},"page":"703-715","source":"Crossref","is-referenced-by-count":16,"title":["Heterozygous cystinuria and urinary lithiasis"],"prefix":"10.1002","volume":"22","author":[{"given":"Roberto","family":"Giugliani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewis J.","family":"Greene","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Opitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James F.","family":"Reynolds","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":"10.3109\/00365597509134221"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(68)90359-X"},{"key":"e_1_2_1_4_1","volume-title":"Statistical Methods in Medical Research","author":"Armitage P","year":"1971"},{"key":"e_1_2_1_5_1","first-page":"345","article-title":"Cystinuria in Sweden. 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