{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T14:59:11Z","timestamp":1775141951287,"version":"3.50.1"},"reference-count":15,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T00:00:00Z","timestamp":1606435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Context<\/jats:title>\n                  <jats:p>Congenital adrenal hyperplasia due to 21-hydroxylase deficiency presents with different severities that correlate with the genotype. The salt-losing phenotype requires 2 alleles with \u201csevere\u201d mutations.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Case Description<\/jats:title>\n                  <jats:p>We present a case of salt-losing 21-hydroxylase deficiency that was found to be homozygous for 2 \u201cmild\u201d pathogenic variants: V281L and S301Y. Both in silico and heterologous expression functional analysis demonstrated that co-occurrence of these 2 mutations in cis severely impairs the function of the 21-hydroxylase enzyme.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This case has important implications for genetic counseling. Regarding this combination of 2 \u201cmild\u201d variants as having mild phenotypic effects could lead to inappropriate counseling of heterozygote carriers.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgaa875","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T19:06:45Z","timestamp":1606504005000},"page":"e680-e686","source":"Crossref","is-referenced-by-count":4,"title":["Salt-Losing 21-Hydroxylase Deficiency Caused by Double Homozygosity for Two \u201cMild\u201d Mutations"],"prefix":"10.1210","volume":"106","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9208-3648","authenticated-orcid":false,"given":"Jacob","family":"Ilany","sequence":"first","affiliation":[{"name":"Institute of Endocrinology, Sheba Medical Center, Tel-Hashomer, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayan","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology, and Diabetes, Departments of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Welsch","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Goethe University Hospital-Frankfurt, Frankfurt am Main, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haike","family":"Reznik-Wolf","sequence":"additional","affiliation":[{"name":"Genetics laboratory, Danek Gartner Institute, Sheba Medical Center, Tel-Hashomer, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ephrat","family":"Levy-Lahad","sequence":"additional","affiliation":[{"name":"Medical Genetics Institute, Shaare Zedek Medical Center, Jerusalem, Israel"},{"name":"Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-6181","authenticated-orcid":false,"given":"Richard J","family":"Auchus","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology, and Diabetes, Departments of Internal Medicine and Pharmacology, University of Michigan, Ann Arbor, MI USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"80","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"issue":"11","key":"2021122206015176000_CIT0001","doi-asserted-by":"crossref","first-page":"4043","DOI":"10.1210\/jc.2018-01865","article-title":"Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an endocrine society clinical practice guideline","volume":"103","author":"Speiser","year":"2018","journal-title":"J Clin Endocrinol 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