AUTHOR=Tolba Aisha , Mandour Iman , Musa Noha , Elmougy Fatma , Hafez Mona , Abdelatty Sahar , Ibrahim Amany , Soliman Hend , Labib Bahaaeldin , Elshiwy Yasmine , Ramzy Tarek , Elsharkawy Marwa 

TITLE=Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children

JOURNAL=Frontiers in Genetics

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.785570

DOI=10.3389/fgene.2022.785570

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Congenital adrenal hyperplasia (CAH) is a monogenic disorder caused by genetic diversity in the <italic>CYP21A2</italic> gene, with 21-hydroxylase deficiency (21-OHD) as the most common type. Early sex assignment and early diagnosis of different genetic variations with a proper technique are important to reduce mortality and morbidity. Proper early sex identification reduces emotional, social, and psychological stress.</p><p><bold>Aim:</bold> Detection of a spectrum of aberrations in the <italic>CYP21A2</italic> gene, including copy number variations, gene conversion, chimeric genes, and point variations.</p><p><bold>Methods:</bold> The <italic>CYP21A2</italic> gene was screened using MLPA assay in 112 unrelated Egyptian children with 21-OHD CAH (33 males and 79 females).</p><p><bold>Results:</bold> In the studied group, 79.5% were diagnosed within the first month of life. 46.8% of the genetic females were misdiagnosed as males. Among the copy number variation results, large deletions in 15.4% and three types of chimeric genes in 9% (CH-1, CH-7, and CAH-X CH-1) were detected. Regarding gene dosage, one copy of <italic>CYP21A2</italic> was found in 5 cases (4.5%), three copies were detected in 7 cases (6.3%), and one case (0.9%) showed four copies. Eight common genetic variants were identified, I2G, large deletions, large gene conversion (LGC), I172N, F306 + T, -113 SNP, 8bp Del, and exon 6 cluster (V237E and M239K) with an allelic frequency of 32.62%, 15.45%, 7.30%, 3.00%, 2.58%, 2.15%, 0.86%, and 0.86%, respectively.</p><p><bold>Conclusion:</bold> High prevalence of copy number variations highlights the added value of using MLPA in routine laboratory diagnosis of CAH patients.</p>