{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T15:54:12Z","timestamp":1779119652896,"version":"3.51.4"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"03","funder":[{"name":"Grants from FAPESP (Funda\u00e7\u00e3o de Amparo a Pesquisa do Estado de Sao Paulo","award":["07\/58365\u20133"],"award-info":[{"award-number":["07\/58365\u20133"]}]},{"name":"CNPq (Brazilian National Council for Research","award":["461125\/2014\u20135"],"award-info":[{"award-number":["461125\/2014\u20135"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Horm Metab Res"],"published-print":{"date-parts":[[2020,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>17-Hydroxylase-deficiency (17OHD) is a rare form of congenital adrenal\n                        hyperplasia. The aim of the work was to study clinical, biochemical, and the\n                        follow up of 17OHD patients and evaluate the function and structure of\n                            CYP17A1 mutations. Brazilian patients (three 46, XX and four 46,\n                        XY; 17\u00b11.9 years) with combined 17-hydroxylase\/17,20-lyase\n                        deficiency were evaluated. CYP17A1 gene was sequenced. Functional\n                        analysis was performed transfecting COS7 cells, which were exposed to\n                        progesterone or 17\u03b1-hydroxypregnolone substrates. Hormones were\n                        determined by RIA or LC-MS\/MS. Three-dimensional structural modeling\n                        was performed by Modeller software. All patients presented prepubertal\n                        female external genitalia, primary amenorrhea, hypergonadotrophic\n                        hypogonadism, hypokalemic hypertension, decreased cortisol, and increased\n                        ACTH and corticosterone levels. Five patients presented previously described\n                        mutations: p.W406R\/p.W406R,\n                        IVS2\u20132A&gt;C\/p.P428L, and p.P428L\/p.P428L. Two\n                        patients presented the compound heterozygous\n                        p.G478S\/p.I223Nfs*10 mutations, whose CYP17A1 activity and\n                        the three dimensional structural modeling are originally studied in this\n                        paper. CYP17A1 activity of p.G478S was 13 and 58% against\n                        progesterone and 17-hydroxypregnenolone, respectively. The\n                        p.I223Nfs*10 caused a truncated inactive protein. Three-dimensional\n                        p.G478S structural modeling showed different internal hydrophobic\n                        interaction with W313 and created an additional chain side contact with L476\n                        residue. Due to the rarity of 17OHD, the long term follow up\n                        (15.3\u00b13.1 years) of our patients will help endocrinologists on the\n                        management of patients with 17OHD. The mutation\n                        p.G478S\/pI223Nfs*10 led to severe 17OHD and impaired CYP17A1\n                        structure and function. The integration of in silico and in vitro analysis\n                        showed how the amino acid changes affected the CYP17A1 activity and\n                        contributed to clarify the molecular interactions of CYP17A1.<\/jats:p>","DOI":"10.1055\/a-1100-7066","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T01:42:49Z","timestamp":1585186969000},"page":"186-193","source":"Crossref","is-referenced-by-count":10,"title":["Clinical, Molecular, Functional, and Structural Characterization of\n                        CYP17A1 Mutations in Brazilian Patients with 17-Hydroxylase\n                    Deficiency"],"prefix":"10.1055","volume":"52","author":[{"given":"Fernanda Borchers","family":"Coeli-Lacchini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Livia M.","family":"Mermejo","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aline Faccioli","family":"Bodoni","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucila Leico Kagohara","family":"Elias","sequence":"additional","affiliation":[{"name":"Department of Physiology, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9364-2886","authenticated-orcid":false,"given":"Wilson Ara\u00fajo","family":"Silva Jr","sequence":"additional","affiliation":[{"name":"Department of Genetics, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonir R.","family":"Antonini","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayrton C.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"de Castro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ribeirao Preto Medical School, University of\n                    Sao Paulo, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,3,25]]},"container-title":["Hormone and Metabolic Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-1100-7066.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T01:43:07Z","timestamp":1585186987000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-1100-7066"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3]]},"references-count":0,"journal-issue":{"issue":"03","published-online":{"date-parts":[[2020,3,25]]},"published-print":{"date-parts":[[2020,3]]}},"URL":"https:\/\/doi.org\/10.1055\/a-1100-7066","relation":{},"ISSN":["0018-5043","1439-4286"],"issn-type":[{"value":"0018-5043","type":"print"},{"value":"1439-4286","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3]]}}}