The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population
ObjectiveCongenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the CYP21A2 gene. After a high prevalence of classic 21-OHD CAH in the Romani population was reported in the Republic of North Macedonia...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1170449/full |
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| author | Katja K. Dumic Zorana Grubic Vesna Kusec Duje Braovac Kristina Gotovac Maja Vinkovic Maja Vucinic Miroslav Dumic |
| author_facet | Katja K. Dumic Zorana Grubic Vesna Kusec Duje Braovac Kristina Gotovac Maja Vinkovic Maja Vucinic Miroslav Dumic |
| author_sort | Katja K. Dumic |
| collection | DOAJ |
| description | ObjectiveCongenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the CYP21A2 gene. After a high prevalence of classic 21-OHD CAH in the Romani population was reported in the Republic of North Macedonia, we decided to estimate the prevalence of 21-OHD in Croatia and, if high, assess the possible causes and estimate the frequency of particular CYP21A2 variants.DesignCross-sectional study.MethodsData from a Croatian 21-OHD genetic database was reviewed, and only Romani patients were included in the study. CYP21A2 genotyping was performed using allele-specific PCR, MLPA, and Sanger sequencing.ResultsAccording to a survey conducted in 2017, Croatia had 22,500 Romani people and six of them had a salt-wasting (SW) form of 21-OHD. All were homozygous for the c.IVS2-13A/C-G pathological variant in intron 2 and descended from consanguineous families belonging to different Romani tribes. The calculated prevalence of 21-OHD in Croatian Romani is 1:3,750, while in the Croatian general population, it is 1:18,000. Three of the six Romani patients originated from two neighboring villages in North-western Croatia (Slavonia County), as well as the seventh patient who is of mixed Romani/Croatian descent and heterozygous for the c.IVS2-13A/C-G pathological variant (not included in the prevalence calculation).ConclusionA high prevalence of SW 21-OHD in the Croatian Romani population caused by the homozygous cIVS2-13A/C-G pathological variant was found. In addition to isolation and consanguinity, other possible reasons could be the heterozygous advantage of the CYP21A2 gene pathological variant and the bottleneck effect as a result of the Romani Holocaust in World War II. |
| first_indexed | 2024-03-13T08:18:11Z |
| format | Article |
| id | doaj.art-e78401ebd2f44716a9af33ec243da054 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-13T08:18:11Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-e78401ebd2f44716a9af33ec243da0542023-05-31T13:42:51ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-05-011410.3389/fendo.2023.11704491170449The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani populationKatja K. Dumic0Zorana Grubic1Vesna Kusec2Duje Braovac3Kristina Gotovac4Maja Vinkovic5Maja Vucinic6Miroslav Dumic7Department of Paediatric Endocrinology and Diabetes, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, CroatiaTissue Typing Centre, Department of Transfusion Medicine and Transplantation Biology, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, CroatiaDepartment of Laboratory Medicine, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, CroatiaDepartment of Paediatric Endocrinology and Diabetes, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, CroatiaDepartment for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb School of Medicine, University Hospital Center Zagreb, Zagreb, CroatiaDepartment of Paediatric Endocrinology and Diabetes, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, CroatiaDepartment of Pediatrics, General Hospital Našice, Našice, CroatiaDepartment of Paediatric Endocrinology and Diabetes, University Hospital Centre Zagreb, University of Zagreb School of Medicine, Zagreb, CroatiaObjectiveCongenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the CYP21A2 gene. After a high prevalence of classic 21-OHD CAH in the Romani population was reported in the Republic of North Macedonia, we decided to estimate the prevalence of 21-OHD in Croatia and, if high, assess the possible causes and estimate the frequency of particular CYP21A2 variants.DesignCross-sectional study.MethodsData from a Croatian 21-OHD genetic database was reviewed, and only Romani patients were included in the study. CYP21A2 genotyping was performed using allele-specific PCR, MLPA, and Sanger sequencing.ResultsAccording to a survey conducted in 2017, Croatia had 22,500 Romani people and six of them had a salt-wasting (SW) form of 21-OHD. All were homozygous for the c.IVS2-13A/C-G pathological variant in intron 2 and descended from consanguineous families belonging to different Romani tribes. The calculated prevalence of 21-OHD in Croatian Romani is 1:3,750, while in the Croatian general population, it is 1:18,000. Three of the six Romani patients originated from two neighboring villages in North-western Croatia (Slavonia County), as well as the seventh patient who is of mixed Romani/Croatian descent and heterozygous for the c.IVS2-13A/C-G pathological variant (not included in the prevalence calculation).ConclusionA high prevalence of SW 21-OHD in the Croatian Romani population caused by the homozygous cIVS2-13A/C-G pathological variant was found. In addition to isolation and consanguinity, other possible reasons could be the heterozygous advantage of the CYP21A2 gene pathological variant and the bottleneck effect as a result of the Romani Holocaust in World War II.https://www.frontiersin.org/articles/10.3389/fendo.2023.1170449/fullcongenital adrenal hyperplasiafounder mutationRomani tribesconsanguinityCYP21A2 heterozygous advantageRomani Holocaust |
| spellingShingle | Katja K. Dumic Zorana Grubic Vesna Kusec Duje Braovac Kristina Gotovac Maja Vinkovic Maja Vucinic Miroslav Dumic The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population Frontiers in Endocrinology congenital adrenal hyperplasia founder mutation Romani tribes consanguinity CYP21A2 heterozygous advantage Romani Holocaust |
| title | The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population |
| title_full | The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population |
| title_fullStr | The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population |
| title_full_unstemmed | The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population |
| title_short | The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population |
| title_sort | prevalence and genotype of 21 hydroxylase deficiency in the croatian romani population |
| topic | congenital adrenal hyperplasia founder mutation Romani tribes consanguinity CYP21A2 heterozygous advantage Romani Holocaust |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1170449/full |
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