Analysis of CYP21A2 gene mutations in patients from Ukraine with congenital adrenal hyperplasia

Congenital adrenal hyperplasia is a group of autosomal recessive disorders. The most frequent one is 21-hydroxylase deficiency. Analyzing CYP21A2 gene mutations was so far not reported in Iraq. This work aims to analyze the spectrum and frequency of CYP21A2 mutations among Iraqi CAH patients. Sixty-two children were recruited from the Pediatric Endocrine Consultation Clinic, Children Welfare Teaching Hospital, Baghdad, Iraq, from September 2014 till June 2015. Their ages ranged between one day and 15 years. They presented with salt wasting, simple virilization, or pseudoprecocious puberty. Cytogenetic study was performed for cases with ambiguous genitalia. Molecular analysis of CYP21A2 gene was done using the CAH StripAssay (ViennaLab Diagnostics) for detection of 11 point mutations and >50% of large gene deletions/conversions. Mutations were found in 42 (67.7%) patients; 31 (50%) patients were homozygotes, 9 (14.5%) were heterozygotes, and 2 (3.2%) were compound heterozygotes with 3 mutations, while 20 (32.3%) patients had none of the tested mutations. The most frequently detected mutations were large gene deletions/conversions found in 12 (19.4%) patients, followed by I2Splice and Q318X in 8 (12.9%) patients each, I172N in 5 (8.1%) patients, and V281L in 4 (6.5%) patients. Del 8 bp, P453S, and R483P were each found in one (1.6%) and complex alleles were found in 2 (3.2%). Four point mutations (P30L, Cluster E6, L307 frameshift, and R356W) were not identified in any patient. In conclusion, gene deletions/conversions and 7 point mutations were recorded in varying proportions, the former being the commonest, generally similar to what was reported in regional countries.

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Comprehensive Genetic Testing of CYP21A2: A Retrospective Analysis in Patients with Suspected Congenital Adrenal Hyperplasia

Journal of Clinical Medicine ◽

10.3390/jcm10061183 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1183

Author(s):

Madalina Nicoleta Nan ◽

Rosa Roig ◽

Susana Martínez ◽

Jose Rives ◽

Eulàlia Urgell ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Point Mutations ◽

Gene Mutations ◽

Pathogenic Variant ◽

Adrenal Hyperplasia ◽

Cyp21a2 Gene ◽

Pathogenic Variants ◽

New Variant ◽

Allelic Distribution ◽

Large Rearrangements

The most common form of congenital adrenal hyperplasia (CAH) results from a deficiency of the 21-hydroxylase enzyme (21-OHD), presenting with a broad spectrum of clinical phenotypes according to the CYP21A2 gene mutations. Of the 59 patients with suspected CAH, 62.7% presented a positive genetic result. Of them, 78.4% and 18.9% presented with non-classical and classical forms, respectively. An overall phenotype-genotype correlation of 88.9% was observed. Biochemically, 17-hydroxiprogesterone concentrations were significantly higher in genetically confirmed patients. Genetically, 36 patients presented with previously reported pathogenic variants, and one presented a new variant in homozygosis. Among the 74 alleles tested, point mutations were found in 89.2% and large rearrangements were found in the rest. The most prevalent pathogenic variant was p.(Val282Leu). The inclusion of relatives revealed one further case. Interestingly, 87.5% of relatives were carriers of a pathogenic variant, including two siblings initially classified as genetically positive. In addition, the study of male partners with gestational desire identified several carriers of mild mutations. Studying the allelic distribution of the variants also allowed for reclassifying one patient. In conclusion, a genetic approach including Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA) analysis, and allelic distribution of the pathogenic variants represents a beneficial tool for better classifying patients with 21-OHD.

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ANALYSIS CYP21A2 GENE MUTATIONS TECHNIQUE IN PATIENTS WITH CONGENITAL ADRENAL HYPERPLASIA

Biotechnologia Acta ◽

10.15407/biotech7.01.075 ◽

2014 ◽

Vol 7 (1) ◽

pp. 75-79 ◽

Cited By ~ 1

Author(s):

S. Yu. Chernushyn ◽

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Gene Mutations ◽

Adrenal Hyperplasia ◽

Cyp21a2 Gene

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Characterization of CYP21A2 Gene Mutations in Dominican Subjects with Congenital Adrenal Hyperplasia.

10.1210/endo-meetings.2010.part1.p7.p1-314 ◽

2010 ◽

pp. P1-314-P1-314

Author(s):

C Tan ◽

JL Imperato-McGinley ◽

I Labour ◽

JJ Cordero ◽

C Montero ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Gene Mutations ◽

Adrenal Hyperplasia ◽

Cyp21a2 Gene

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The spectrum of CYP21A2 gene mutations in patients with 2l-hydroxylase deficiency -induced congenital adrenal hyperplasia in a Chinese cohort

10.21203/rs.3.rs-19624/v1 ◽

2020 ◽

Author(s):

Yang Liu ◽

Jie Zheng ◽

Xiaowei Xu ◽

Xinjie Zhang ◽

Ying Zhang ◽

...

Keyword(s):

Congenital Adrenal Hyperplasia ◽

Gene Mutations ◽

Autosomal Recessive Disorder ◽

Northern China ◽

Molecular Data ◽

Adrenal Hyperplasia ◽

Hydroxylase Deficiency ◽

Cyp21a2 Gene ◽

Large Gene ◽

21 Hydroxylase Deficiency

Abstract Background 21-hydroxylase deficiency (21-OHD) caused by the CYP21A2 gene mutations is the most popular form of congenital adrenal hyperplasia. It is an autosomal recessive disorder results in the defective synthesis of cortisol and aldosterone. The incidences of various CYP21A2 gene mutations and the genotype-phenotype correlations vary among different populations. Therefore, the aim of current study was to identify the spectrum of CYP21A2 gene mutations of patients from northern China and analyze the genotype-phenotype correlation.Methods The clinical and molecular data of 22 patients were analyzed in this study. Locus-specific polymerasechain reaction and Sanger sequencing were applied to identify gene micro-conversions, and multiplex ligation-dependent probe amplification as an alternative to Southern blotting was used to detect large fragment deletions/conversions. Then the genotypes were categorized in to Null, A, B, C and D groups to analyze the relationships between genotypes and phenotypes.Results Molecular defects were detected in 44 alleles (100%). Micro-conversion mutation IVS2-13A/C> G (70.5%) is most common in our cohort, followed by large gene deletions and conversions (22.7%). The other mutations present were p.R357W (4.5%) and E6 Cluster (2.3%). Genotypes of 22 patients (100%) were consistent with the predictive phenotypes.Conclusions In this study, we collected 22 21-OHD patients’ clinical and mutations data in Chinese population, especially in northern China. Micro-conversions were the most popular mutations and the frequencies were consistent with other cohorts. Moreover, thegenotypes and phenotypes in 21-OHDwere well correlated. This studyidentifiedthe mutation spectrum of CYP21A2gene and conduced to genetic counseling and prenatal diagnosis.

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