Tolba, A., I. Mandour, N. Musa, F. E. Mougy, M. Hafez, S. A. E. Atty, A. Ibrahim, H. Soliman, B. Labib, Y. Elshiwy, et al., "Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children.", Frontiers in genetics, vol. 13, pp. 1-8, 2022. Abstract

Congenital adrenal hyperplasia (CAH) is a monogenic disorder caused by genetic diversity in the 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. Detection of a spectrum of aberrations in the gene, including copy number variations, gene conversion, chimeric genes, and point variations. The gene was screened using MLPA assay in 112 unrelated Egyptian children with 21-OHD CAH (33 males and 79 females). 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 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. High prevalence of copy number variations highlights the added value of using MLPA in routine laboratory diagnosis of CAH patients.

Elmougy, F., M. Elsharkawy, M. Hafez, S. A. Atty, H. Baz, A. Ibrahim, H. Soliman, S. Ekladious, M. Abdullatif, G. Thabet, et al., "Genetic profiling of CAH Egyptian children: rapid guide to clinical interpretation of common mutations.", Journal of endocrinological investigation, vol. 44, issue 1, pp. 83-93, 2021. Abstract

OBJECTIVES: The prevalence of CAH in Egypt is reported to be ten times more than that of the worldwide prevalence. The study aimed at genetic screening of children diagnosed with 21-alpha hydroxylase deficiency congenital adrenal hyperplasia (21OHD-CAH). In addition, the study offers a rapid and easy guide for clinical reporting of common mutations for endocrinologists.

METHODS: A cohort of 174 unrelated Egyptian children with 21OHD-CAH were screened for 11 common CYP21A2 gene mutations using a strip hybridization assay, and then, bioinformatics analysis was done to report the pathogenicity of the common mutations for clinical classification.

RESULTS: The most common mutations were I2 splice and p.Q318X. Deletions/conversions comprised 45.9% of the cohort, whereas 7.4% of the cases were negative for all mutations. The least positively detected point mutations were p.P453S, cluster E6, p.R483P, and p.L307FS, which were detected in fewer than 5% of cases.

CONCLUSION: Strip hybridization assay is a rapid screening tool for the diagnosis of CAH. The authors hypothesized an easy and rapid scheme for clinical interpretation of the strip results to gain the highest value of the strip in diagnosis.

Gohar, N. A., W. A. Rabie, S. A. Sharaf, M. M. Elsharkawy, M. F. Mira, A. O. Tolba, and H. Aly, "Identification of insulin gene variants in neonatal diabetes.", The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, vol. 30, issue 9, pp. 1035-1040, 2017. Abstract

OBJECTIVES: Permanent neonatal diabetes (PNDM) is caused by mutations in the genes responsible for the synthesis of different proteins that are important for the normal behavior of beta cells in the pancreas. Mutations in the insulin gene (INS) are considered as one of the causes of diabetes in neonates. This study aimed to investigate the genetic variations in the INS gene in a group of Egyptian infants diagnosed with PNDM.

METHODS: We screened exons 2 and 3 with intronic boundaries of the INS gene by direct gene sequencing in 30 PNDM patients and 20 healthy controls. A detailed clinical phenotyping of the patients was carried out to specify the diabetes features in those found to carry an INS variant.

RESULTS: We identified five variants (four SNPs and one synonymous variant), c(0).187 + 11T > C, c.-17-6T > A, c.*22A > C, c.*9C > T, and c.36G > A (p.A12A), with allelic frequencies of 96.7%, 80%, 75%, 5%, and 1.7%, respectively. All showed no statistically significance difference compared with the controls, with the exception of c.*22A > C.

CONCLUSION: Genetic screening for the INS gene did not reveal an evident role in the diagnosis of PNDM.

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