The prevalence and genotype of 21-hydroxylase deficiency in the Croatian Romani population

• Published in: Frontiers in endocrinology (Lausanne) Vol. 14; p. 1170449
• Main Authors: Dumic, Katja K, Grubic, Zorana, Kusec, Vesna, Braovac, Duje, Gotovac, Kristina, Vinkovic, Maja, Vucinic, Maja, Dumic, Miroslav
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 31.05.2023
• Subjects: Adrenal Hyperplasia, Congenital - epidemiology; Adrenal Hyperplasia, Congenital - genetics; congenital adrenal hyperplasia; consanguinity; Croatia - epidemiology; Cross-Sectional Studies; CYP21A2 heterozygous advantage; Endocrinology; founder mutation; Genotype; Humans; Prevalence; Roma; Romani Holocaust; Romani tribes; Steroid 21-Hydroxylase - genetics; Croatia; CYP21A2 heterozygous advantage; Romani Holocaust; bottle neck effect; consanguinity; Romani tribes; congenital adrenal hyperplasia; founder mutation
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2023.1170449

Congenital adrenal hyperplasia (CAH) owing to 21-hydroxylase deficiency (21-OHD) is a rare autosomal recessive disorder caused by pathological variants in the 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 variants. Cross-sectional study. Data from a Croatian 21-OHD genetic database was reviewed, and only Romani patients were included in the study. genotyping was performed using allele-specific PCR, MLPA, and Sanger sequencing. According 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). A 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 gene pathological variant and the bottleneck effect as a result of the Romani Holocaust in World War II.