ECE2023 Eposter Presentations Adrenal and Cardiovascular Endocrinology (124 abstracts)
Carriers of a pathological variant in CYP21A2 gene– clinical and hormonal status
Sorina Schipor 1 , Camelia Procopiuc 2 , Cristina Stancu 1 , Madalina Vintila 2,3 , Andreea Cristiana Brehar 2 , Andrei Muresan 1 , Dana Manda 1 , Andra Caragheorgheopol 1 , Dumitrica Alina Elena 1 , Luminita Udrea 1 , Suzana Vladoiu 1 & Iuliana Gherlan 2,3
1National Institute of Endocrinology "C. I. Parhon", Research Department, Romania; 2National Institute of Endocrinology "C. I. Parhon", Paediatric Department, Romania; 3University of Medicine and Pharmacy "Carol Davila", Romania
Introduction: 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder and the diagnosis is confirmed by the presence of at least two biallelic pathogenic variants. The phenotype is determined by the less deleterious variant. The relevance of hormonal assessment to distinguish between heterozygote carriers of pathologic mutations and non-carriers or genetically defined 21OHD patients is still a matter of debate. Identifying the heterozygous genotype is important in adult life for a correct genetic counselling and a personalized approach of future pregnancies.
Materials and methods: We selected a group of Romanian paediatric patients with hyperandrogenism manifested as premature pubarche, accelerated growth, apocrine body odour, and seborrhoea in childhood (n=19) and hirsutism, oligomenorrhoea and acne in adolescence (n=12). 17OH-progesterone levels were measured by ELISA (reference values <2 ng/ml). MLPA and Sanger sequencing were used to establish CYP21A2 gene mutational status. All patients gave their informed consent for the study.
Results and discussion: After molecular analysis we identified 17 carriers of a pathologic variant in CYP21A2 gene (carrier-group) and 14 patients with genetic confirmation of 21OHD (21OHD-group). The pathologic variants identified in the carrier-group were V282L (35.71%), P31L (28.57%), P454S (21.43%), R92* (7.14%) and I173N (7.14%). We also identified 3 patients with heterozygous Q319* mutation but MLPA also revealed heterozygous duplication of CYP21A2 gene so we excluded them from the analysis. Patients included in 21OHD-group were homozygous or compound heterozygous for pathologic variants identified in the carrier-group and the diagnosis was non-classic or simple-virilizing form of 21OHD. 17OH-progesterone levels were significantly lower in carrier-group vs 21OHD-group (median 2.06 ng/ml vs 20 ng/ml). For the carrier-group the values are slightly increased or high-normal compared to kit reference values.
Conclusion: Clinically manifested hyperandrogenism with or without a concomitant increase of 17OH-progesterone could be a criterion for investigation of possible heterozygous carriers of a pathologic variant in CYP21A2 gene in paediatric population.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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