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Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt.
J Pediatr Endocrinol Metab. 2020 Jul 28; 33(7):893-900.JP

Abstract

Objectives Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder caused by defects in the CYP21A2 gene. We aimed to determine the prevalence of the most commonly reported mutations among 21-OHD Egyptian patients and correlate genotype with phenotype. Methods Molecular analysis of the CYP21A2 gene was performed for the detection of the six most common point mutations (p.P30L, p.I172N, p.V281L, p.Q318X, the splice site mutation Int2 [IVS2-13A/C>G], and the cluster of three mutations [p.I236N, p.V237E, and p.M239K] designed as CL6). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed on 47 unrelated Egyptian 21α-OH deficiency patients and their available parents to detect the presence of the six most common point mutations. Results Screening for the six most common point mutations in CYP21A2 gene, revealed mutations in 87.2% (82/94) of the studied alleles corresponding to 47 Egyptian patients. The most common mutation among the studied cases was IVS2-13C/A>G that was found to be presented in a frequency of 46.8% (44/94). The genotype/phenotype correlations related to null, A, and B groups were with PPV of 100, 55.5, and 83.3%, respectively. Conclusions The described method diagnosed CAH in 80.8% of the studied patients. Good correlation between genotype and phenotype in salt wasting and simple virilizing forms is determined, whereas little concordance is seen in nonclassical one. Furthermore, studying the carrier frequency of 21-OHD among the normal population is of great importance.

Authors+Show Affiliations

Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt.Clinical Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt.Diabetes, Endocrinology & Metabolic Pediatric Unit, Cairo University, Cairo, Egypt.Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt.Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt.Division of Paediatric Endocrinology & Diabetes, Department of Paediatrics, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt.Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt.Zoology Department, Faculty of Science, Cairo University, Cairo, Egypt.Division of Paediatric Endocrinology & Diabetes, Department of Paediatrics, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.Medical Molecular Genetics Department, Division of Human Genetics and Genome Research, National Research Centre, Cairo, Egypt.Division of Paediatric Endocrinology & Diabetes, Department of Paediatrics, Christian-Albrechts-Universität zu Kiel, Kiel, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32614782

Citation

Essawi, Mona, et al. "Assessment of the Most Common CYP21A2 Point Mutations in a Cohort of Congenital Adrenal Hyperplasia Patients From Egypt." Journal of Pediatric Endocrinology & Metabolism : JPEM, vol. 33, no. 7, 2020, pp. 893-900.
Essawi M, Mazen I, Fawaz L, et al. Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt. J Pediatr Endocrinol Metab. 2020;33(7):893-900.
Essawi, M., Mazen, I., Fawaz, L., Hassan, H., ElBagoury, N., Peter, M., Gaafar, K., Amer, M., Nabil, W., Hohmann, G., Soliman, H., & Sippell, W. (2020). Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt. Journal of Pediatric Endocrinology & Metabolism : JPEM, 33(7), 893-900. https://doi.org/10.1515/jpem-2019-0575
Essawi M, et al. Assessment of the Most Common CYP21A2 Point Mutations in a Cohort of Congenital Adrenal Hyperplasia Patients From Egypt. J Pediatr Endocrinol Metab. 2020 Jul 28;33(7):893-900. PubMed PMID: 32614782.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Assessment of the most common CYP21A2 point mutations in a cohort of congenital adrenal hyperplasia patients from Egypt. AU - Essawi,Mona, AU - Mazen,Inas, AU - Fawaz,Lubna, AU - Hassan,Heba, AU - ElBagoury,Nagham, AU - Peter,Michael, AU - Gaafar,Khadiga, AU - Amer,Mahmoud, AU - Nabil,Wajeet, AU - Hohmann,Gisela, AU - Soliman,Hala, AU - Sippell,Wolfgang, PY - 2019/12/13/received PY - 2020/05/08/accepted PY - 2020/7/3/pubmed PY - 2021/5/29/medline PY - 2020/7/3/entrez KW - CYP21A2 KW - CAH KW - genotype KW - phenotype KW - point mutations SP - 893 EP - 900 JF - Journal of pediatric endocrinology & metabolism : JPEM JO - J Pediatr Endocrinol Metab VL - 33 IS - 7 N2 - Objectives Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is a common autosomal recessive disorder caused by defects in the CYP21A2 gene. We aimed to determine the prevalence of the most commonly reported mutations among 21-OHD Egyptian patients and correlate genotype with phenotype. Methods Molecular analysis of the CYP21A2 gene was performed for the detection of the six most common point mutations (p.P30L, p.I172N, p.V281L, p.Q318X, the splice site mutation Int2 [IVS2-13A/C>G], and the cluster of three mutations [p.I236N, p.V237E, and p.M239K] designed as CL6). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed on 47 unrelated Egyptian 21α-OH deficiency patients and their available parents to detect the presence of the six most common point mutations. Results Screening for the six most common point mutations in CYP21A2 gene, revealed mutations in 87.2% (82/94) of the studied alleles corresponding to 47 Egyptian patients. The most common mutation among the studied cases was IVS2-13C/A>G that was found to be presented in a frequency of 46.8% (44/94). The genotype/phenotype correlations related to null, A, and B groups were with PPV of 100, 55.5, and 83.3%, respectively. Conclusions The described method diagnosed CAH in 80.8% of the studied patients. Good correlation between genotype and phenotype in salt wasting and simple virilizing forms is determined, whereas little concordance is seen in nonclassical one. Furthermore, studying the carrier frequency of 21-OHD among the normal population is of great importance. SN - 2191-0251 UR - https://www.unboundmedicine.com/medline/citation/32614782/Assessment_of_the_most_common_CYP21A2_point_mutations_in_a_cohort_of_congenital_adrenal_hyperplasia_patients_from_Egypt_ L2 - https://www.degruyter.com/document/doi/10.1515/jpem-2019-0575 DB - PRIME DP - Unbound Medicine ER -