{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T05:10:37Z","timestamp":1698642637008},"reference-count":14,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2001,12,24]],"date-time":"2001-12-24T00:00:00Z","timestamp":1009152000000},"content-version":"vor","delay-in-days":449,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2000,10]]},"abstract":"<jats:sec><jats:title>OBJECTIVES<\/jats:title><jats:p>Congenital adrenal hyperplasia (CAH) is a common endocrine disorder and CYP21 (21\u2010OH, EC 1.14.99.10) deficiency is the most common cause of the disease. The presence of a pseudogene and a wide range of mutation types often makes DNA diagnosis difficult. Analysis of mutant alleles from patients with CAH identified a new DNA polymorphism in exon 10. To test the usefulness of this polymorphism, linkage analysis was performed using three RFLP's at both end of the CYP21 gene in patients and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>DESIGN AND PATIENTS<\/jats:title><jats:p>Genomic DNA was extracted from 21 unrelated patients and 39 unaffected individuals. Haplotyping analysis was performed for three RFLPs, <jats:italic>Msp<\/jats:italic>I and <jats:italic>Fnu4H<\/jats:italic>I in intron 2 and a new <jats:italic>Sma<\/jats:italic>I RFLP in exon 10. All three polymorphic sites were characterized by DNA sequencing and usefulness of these RFLPs for DNA diagnosis was tested in patients' families.<\/jats:p><\/jats:sec><jats:sec><jats:title>MEASUREMENT<\/jats:title><jats:p>CAH patients were diagnosed by clinical symptoms and biochemical tests. Allele frequencies and heterozygosities were studied for three RFLP's in patients and controls using polymerase chain reaction (PCR).<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>A new <jats:italic>Sma<\/jats:italic>I RFLP showed a sequence difference as G or A at the nucleotide position 2694 in exon 10. Sequences at the <jats:italic>Msp<\/jats:italic>I and <jats:italic>Fnu<\/jats:italic>4HI polymorphic sites were T or C at the nucleotide position 395 and 453, respectively. All of these RFLPs showed biallelic DNA polymorphisms and codominant segregation in family analysis. Heterozygosities were 0.31 for <jats:italic>Msp<\/jats:italic>I, 0.48 for <jats:italic>Fnu<\/jats:italic>4HI and 0.44 for <jats:italic>Sma<\/jats:italic>I in normal individuals. There was no linkage disequilibrium for three RFLPs between patients and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>The <jats:italic>Sma<\/jats:italic>I RFLP can be useful for linkage analysis and DNA diagnosis in conjunction with RFLPs in intron 2 in CAH families because the polymorphic site is within the active gene at the 3\u2032 end. DNA sequencing results revealed that these RFLPs were created by gene conversions as with other mutations in the CYP21 gene.<\/jats:p><\/jats:sec>","DOI":"10.1046\/j.1365-2265.2000.01090.x","type":"journal-article","created":{"date-parts":[[2003,3,11]],"date-time":"2003-03-11T10:46:30Z","timestamp":1047379590000},"page":"419-422","source":"Crossref","is-referenced-by-count":2,"title":["Characterization of a novel DNA polymorphism in the human CYP21 gene and application for DNA diagnosis of congenital adrenal hyperplasia"],"prefix":"10.1111","volume":"53","author":[{"given":"Yong\u2010Ho","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eun\u2010Sook","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shin\u2010Hye","family":"Kang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hogeun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin\u2010Yong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin\u2010Sung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,12,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.2.521"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/5.12.2039"},{"key":"e_1_2_6_4_1","first-page":"17","article-title":"Evidence for frequent gene conversion in the steroid 21\u2010hydroxylase P450 (C21) gene: implications for steroid 21\u2010hydroxylase deficiency","volume":"42","author":"Higashi Y.","year":"1988","journal-title":"American Journal of Human Genetics"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.9.2841"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.23.120189.002103"},{"key":"e_1_2_6_7_1","unstructured":"New M.I. White P.C. Pang S. Dupont B. Speiser P.W.(1989) The adrenal hyperplasias. InThe Metabolic Basis of Inherited Disease(Scriver C.R. Beaudet A.L. Sly W.S. Valle D. eds.) pp.18811918 McGraw\u2010Hill New York."},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1987.tb02414.x"},{"key":"e_1_2_6_9_1","unstructured":"Sambrook J. Fritch E.F. Maniatis T.(1989) Molecular cloning.A Laboratory Manual2nd edn. Cold Spring Harbor Laboratory Cold Spring Harbor."},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/2.5.499"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00218263"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.15.7232"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.82.4.1089"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.14.5111"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198706113162406"}],"container-title":["Clinical Endocrinology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2265.2000.01090.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1046%2Fj.1365-2265.2000.01090.x","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1046\/j.1365-2265.2000.01090.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,29]],"date-time":"2023-10-29T18:33:55Z","timestamp":1698604435000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1046\/j.1365-2265.2000.01090.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2000,10]]},"references-count":14,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2000,10]]}},"alternative-id":["10.1046\/j.1365-2265.2000.01090.x"],"URL":"https:\/\/doi.org\/10.1046\/j.1365-2265.2000.01090.x","archive":["Portico"],"relation":{},"ISSN":["0300-0664","1365-2265"],"issn-type":[{"value":"0300-0664","type":"print"},{"value":"1365-2265","type":"electronic"}],"subject":[],"published":{"date-parts":[[2000,10]]}}}