AI Article Synopsis
- This study focused on identifying genetic variants in 500 Greek individuals suspected of having 21-hydroxylase deficiency (21-OHD), a common form of congenital adrenal hyperplasia, by using gene sequencing and MLPA techniques.* -
- Genetic diagnoses were confirmed in 27.4% of the cases, with a notable portion of subjects displaying the non-classic form of 21-OHD, and 42.6% being heterozygotes; however, 27% exhibited no identifiable pathogenic variants.* -
- The study suggested that measuring the change in 17-hydroxyprogesterone levels post-ACTH stimulation might serve as a potential biomarker to differentiate heterozygotes from those without
Article Abstract
21-hydroxylase deficiency (21-OHD) represents the most common form of congenital adrenal hyperplasia (CAH) due to gene pathogenic variants. Τhe aim of this study was the identification of variants in 500 subjects of Greek origin with a suspicion of 21-OHD and, by using the existing hormonal assessment and genotypes of the 500 subjects tested, to identify a biomarker that could differentiate between the heterozygotes and the cases with no pathogenic variants identified. Five hundred subjects with clinical suspicion of 21-OHD underwent gene sequencing and Multiplex Ligation Dependent Probe Amplification (MLPA). Genetic diagnosis was achieved in 27.4% of the subjects tested, most of which presented with the non-classic form (NC) of 21-OHD. Heterozygotes accounted for 42.6% of cases, whereas no pathogenic variants were identified in 27% of cases. De novo aberrations, duplications, and five novel variants were also identified. Statistical analysis revealed that the difference between the basal and 60' post-ACTH stimulation 17-hydroxyprogesterone concentrations (Δ17-OHP) could be a potential biomarker ( < 0.05) distinguishing the heterozygotes from the cases with no pathogenic variants identified, although no clear cut-off value could be set. Further analysis revealed overlapping clinical manifestations among all the subjects tested. The presented phenotypic traits of the subjects tested and the inability to identify a discriminative biochemical marker highlight the importance of comprehensive genotyping to ascertain the correct genetic diagnosis and proper genetic counselling.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11506624 | PMC |
| http://dx.doi.org/10.3390/cimb46100635 | DOI Listing |
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