{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T22:43:38Z","timestamp":1788043418740,"version":"build-2784847793"},"reference-count":41,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,3,2]],"date-time":"2021-03-02T00:00:00Z","timestamp":1614643200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>21\u2010hydroxylase deficiency (21OHD) is an autosomal recessive disorder with an incidence of 1:10,000\u20101:20,000 and is the result of various mutations in the <jats:italic>CYP21A2<\/jats:italic> gene. 21OHD has been described in many different populations, but it has not been studied in Roma individuals so far. The aim of the study was to analyse the genotype in Roma patients with 21OHD and the prevalence of the disease in the Roma population of North Macedonia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Molecular analysis of the nine most frequent <jats:italic>CYP21A2<\/jats:italic> mutations in all known Roma patients with CAH in North Macedonia, relatives and healthy individuals of Roma ancestry, using the PCR\/ACRS method.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Ten Roma patients with 21OHD were identified, of which nine had the salt\u2010wasting and one had the simple virilizing form. Calculated incidence of 21OHD in the North Macedonian Roma population was 1:3375. Interestingly, 9\/10 patients (90%) were homozygous for the In2G splicing mutation (293\u201013A\/C\u00a0&gt;\u00a0G). Standard therapy with hydrocortisone and fludrocortisone had been introduced according to the guidelines. In 16 healthy relatives investigated for <jats:italic>CYP21A2<\/jats:italic> mutations, heterozygosity for the In2G mutation was detected in 13\/32 (40.6%) alleles. In 100 healthy Roma individuals, none related to the analysed families, no <jats:italic>CYP21A2<\/jats:italic> mutations were detected.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The Roma population in North Macedonia had a very high incidence of classic 21OHD. Almost all patients had the severe salt\u2010wasting form and the In2G\/In2G genotype.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.14447","type":"journal-article","created":{"date-parts":[[2021,2,19]],"date-time":"2021-02-19T10:25:55Z","timestamp":1613730355000},"page":"41-46","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["First insights into the genetics of 21\u2010hydroxylase deficiency in the Roma population"],"prefix":"10.1111","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7097-3439","authenticated-orcid":false,"given":"Mirjana","family":"Kocova","sequence":"first","affiliation":[{"name":"Department of Endocrinology and Genetics University Pediatric Hospital, Skopje University \u201cSs Cyril and Methodius\u201d Skopje Republic of North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violeta","family":"Anastasovska","sequence":"additional","affiliation":[{"name":"Genetic Laboratory University Pediatric Hospital, Skopje University \u201cSs Cyril and Methodius\u201d Skopje Republic of North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1956-4063","authenticated-orcid":false,"given":"Aleksandar","family":"Petlichkovski","sequence":"additional","affiliation":[{"name":"Institute of Immunology and Human genetics Medical Faculty University \u201cSs Cyril and Methodius\u201d Skopje Republic of North Macedonia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5622-6987","authenticated-orcid":false,"given":"Henrik","family":"Falhammar","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Metabolism and Diabetes Karolinska University Hospital Stockholm Sweden"},{"name":"Departement of Molecular Medicine and Surgery Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,3,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2006.12.005"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23351"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1300057110"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31431-9"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-018-0319-y"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-020-02323-3"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-18-0712"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1530\/eje.1.01944"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1515\/JPEM.2004.17.2.157"},{"issue":"6","key":"e_1_2_9_11_1","first-page":"866","article-title":"Worldwide experience in newborn screening for classical congenital adrenal hyperplasia due to 21\u2010hydroxylase deficiency","volume":"81","author":"Pang SY","year":"1988","journal-title":"Pediatrics"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-015-0731-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(13)70007-X"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-1809.2007.00421.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1086\/424759"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2012.10.039"},{"issue":"5","key":"e_1_2_9_17_1","article-title":"Genetic studies in Roma (Gypsies): a review","volume":"2","author":"Kalaydjieva L","year":"2001","journal-title":"BMC Med Genet"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijns3030025"},{"key":"e_1_2_9_19_1","unstructured":"State Statistica Office Republic of Macedonia.Natality of the Republic of Macedonia by the municipality 2011. 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