p.Gln318X and p.Val281Leu as the Major Variants of <i>CYP21A2</i> Gene in Children with Idiopathic Premature Pubarche

Soveizi, Mahdieh; Mahdieh, Nejat; Setoodeh, Aria; Sayarifard, Fatemeh; Abbasi, Farzaneh; Bose, Himangshu S.; Rabbani, Bahareh; Rabbani, Ali

doi:10.1155/2020/4329791

Cited by 2 publications

(2 citation statements)

References 57 publications

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“…Until 2022 several studies have performed genotyping approaches to investigate CYP21A2 alleles in Iranian CAH patients. According to previous studies reviewed in table 3, In2G and Q318X are the most reported mutations in Iranian families [20][21][22][23][24][25][26][27] . Our findings coincide with previous studies.…”

Section: Discussionmentioning

confidence: 99%

CYP21A2 Gene Analysis in Southern Iranian CAH Patients and a Brief Review of the Mutation Spectrum

Zangene,

Moravej,

Ilkhanipoor

et al. 2024

AJMB

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Background: CYP21A2 gene mutations are responsible for more than 95% of Congenital Adrenal Hyperplasia (CAH) disorders with autosomal recessive inheritance. Most of these pathogenic mutations originate from the CYP21A1P, a neighboring pseudogene with 98% homology, due to unequal crossing over or gene conversion events. Mutation identification of the gene could be beneficial for accurate diagnosis and outcome prediction. Methods: Twelve unrelated patients with CAH diagnosis were recruited for genetic counseling. To ensure distinct amplification of the CYP21A2 gene rather than its pseudogene, the complete sequence of the gene was amplified through two overlapping fragments by specific primers. The entire sequences were screened by direct Sanger sequencing using new sequencing primers. Results: Only two pathogenic point mutations were identified. The c.293-13C>G, also known as In2G, and the c.955C>T mutations were found in 37.5 and 33.3% of alleles, respectively. One patient showed homozygous gene deletion. We also reviewed recent reports on CYP21A2 gene mutations in Iran. Conclusion: Evaluating the ethnicity-specific gene mutation data is significant for populations with diverse ethnic groups including the Iranian population. Although several common mutations have been reported as causative mutations among CAH patients, identifying only two common point mutations in Fars province would help prioritize exon sequencing and reduce the cost and time of genotyping.

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Section: Discussionmentioning

confidence: 99%

CYP21A2 Gene Analysis in Southern Iranian CAH Patients and a Brief Review of the Mutation Spectrum

Zangene,

Moravej,

Ilkhanipoor

et al. 2024

AJMB

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“…Individuals homozygous for this mutation have the severe salt-wasting (SW) form of CAH and no enzymatic activity (22,26). Several other reports have also demonstrated that heterozygosity for the p.Gln319Ter variant can be an issue especially in females and that exhibit the milder NC-CAH form (27)(28)(29).…”

Section: Introductionmentioning

confidence: 94%

The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes

et al. 2023

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ObjectiveThe study aimed to identify the pathogenic status of p.Gln319Ter (NM_000500.7: c.955C>T) variant when inherited in a single CYP21A2 gene (bimodular RCCX haplotype) and to discriminate between a non-causing congenital adrenal hyperplasia (CAH) allele when inherited in a duplicated and functional CYP21A2 gene context (trimodular RCCX haplotype).Methods38 females and 8 males with hyperandrogenemia, previously screened by sequencing and identified as carriers for the pathogenic p.Gln319Ter, were herein tested by multiplex ligation-dependent probe amplification (MLPA) and a real-time PCR Copy number Variation (CNV) assay.ResultsBoth MLPA and real-time PCR CNV analyses confirmed a bimodular and pathogenic RCCX haplotype with a single CYP21A2 in 19/46 (41.30%) p.Gln319Ter carriers and who in parallel all shared elevated 17-OHP levels. The remaining 27 individuals that also carried the p.Gln319Ter exhibited low 17-OHP levels as a result of their carriership of a duplicated CYP21A2 with a trimodular RCCX haplotype. Interestingly, all of these individuals also carried in linkage disequilibrium with p.Gln319Ter two single nucleotide polymorphisms, the c.293-79G>A (rs114414746) in intron 2 and the c.*12C>T (rs150697472) in the 3’-UTR. Therefore, these variants can be used to distinguish between pathogenic and non-pathogenic genomic contexts of the c.955T (p.Gln319) in the genetic diagnosis of congenital adrenal hyperplasia (CAH).ConclusionThe employed methodologies identified a considerable number of individuals with non-pathogenic p.Gln319Ter from the individuals that typically carry the pathogenic p.Gln319Ter in a single CYP21A2. Therefore, it is extremely important the detection of such haplotypes for the prenatal diagnosis, treatment and genetic counseling in patients with CAH.

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p.Gln318X and p.Val281Leu as the Major Variants of CYP21A2 Gene in Children with Idiopathic Premature Pubarche

Cited by 2 publications

References 57 publications

CYP21A2 Gene Analysis in Southern Iranian CAH Patients and a Brief Review of the Mutation Spectrum

CYP21A2 Gene Analysis in Southern Iranian CAH Patients and a Brief Review of the Mutation Spectrum

The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes

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