{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T05:32:35Z","timestamp":1763443955315,"version":"3.37.3"},"reference-count":8,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2015,8,20]],"date-time":"2015-08-20T00:00:00Z","timestamp":1440028800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HD00072, AG40132, DK80459, AG23176, AR06592, AR06066"],"award-info":[{"award-number":["HD00072, AG40132, DK80459, AG23176, AR06592, AR06066"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of the New York Academy of Sciences"],"published-print":{"date-parts":[[2016,1]]},"abstract":"<jats:p>Congenital adrenal hyperplasia (CAH) owing to 21\u2010hydroxylase deficiency is caused by the autosomal recessive in\u2010heritance of mutations in the gene <jats:italic>CYP21A2<\/jats:italic>. <jats:italic>CYP21A2<\/jats:italic> mutations lead to variable impairment of the 21\u2010hydroxylase enzyme, which, in turn, is associated with three clinical phenotypes, namely, salt wasting, simple virilizing, and nonclassical CAH. However, it is known that a given mutation can associate with different clinical phenotypes, resulting in a high rate of genotype\u2013phenotype nonconcordance. We aimed to study the genotype\u2013phenotype nonconcordance in a family with three siblings affected with nonclassical CAH. All had hormonal evidence of nonclassical CAH, but this phenotype could not be explained by the genotype obtained from commercial <jats:italic>CYP21A2<\/jats:italic> genetic testing, which revealed heterozygosity for the maternal 30 kb deletion mutation. We performed Sanger sequencing of the entire <jats:italic>CYP21A2<\/jats:italic> gene in this family to search for a rare mutation that was not covered by commercial testing and found in the three siblings a second, rare c.1097G&gt;A (p.R366H) mutation in exon 8. Computational modeling confirmed that this was a mild mutation consistent with nonclassical CAH. We recommend that sequencing of entire genes for rare mutations should be carried out when genotype\u2013phenotype nonconcordance is observed in patients with autosomal recessive monogenic disorders, including CAH.<\/jats:p>","DOI":"10.1111\/nyas.12864","type":"journal-article","created":{"date-parts":[[2015,8,20]],"date-time":"2015-08-20T20:44:58Z","timestamp":1440103498000},"page":"5-10","source":"Crossref","is-referenced-by-count":14,"title":["A rare <i>CYP21A2<\/i> mutation in a congenital adrenal hyperplasia kindred displaying genotype\u2013phenotype nonconcordance"],"prefix":"10.1111","volume":"1364","author":[{"given":"Ahmed","family":"Khattab","sequence":"first","affiliation":[{"name":"Division of Adrenal Steroid Disorders, Department of Pediatrics Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tony","family":"Yuen","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Mount Sinai Bone Program Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sultan","family":"Al\u2010Malki","sequence":"additional","affiliation":[{"name":"Division of Adrenal Steroid Disorders, Department of Pediatrics Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mabel","family":"Yau","sequence":"additional","affiliation":[{"name":"Division of Adrenal Steroid Disorders, Department of Pediatrics Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diya","family":"Kazmi","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Mount Sinai Bone Program Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Mount Sinai Bone Program Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madeleine","family":"Harbison","sequence":"additional","affiliation":[{"name":"Division of Adrenal Steroid Disorders, Department of Pediatrics Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shozeb","family":"Haider","sequence":"additional","affiliation":[{"name":"School of Pharmacy University College  London United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mone","family":"Zaidi","sequence":"additional","affiliation":[{"name":"Department of Medicine, The Mount Sinai Bone Program Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria I.","family":"New","sequence":"additional","affiliation":[{"name":"Division of Adrenal Steroid Disorders, Department of Pediatrics Icahn School of Medicine at Mount Sinai  New York New York"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,8,20]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-416006-4.00003-X"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-57-2-320"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1221133110"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300057110"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-11-0119"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1400788"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2003.11.006"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540150503"}],"container-title":["Annals of the New York Academy of 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