Steroid 21-hydroxylase gene mutational spectrum in 50 Tunisian patients: Characterization of three novel polymorphisms

Charfeddine, Ilhem Ben; Riepe, Felix G.; Clauser, Éric; Ayedi, Abdelkarim; Makni, S.; Sfar, Mohamed Tahar; Sboui, H.; Kahloul, N.; Hamouda, H. Ben; Chouchane, S.; Trimech, Sihem; Zouari, Noura; Mrabet, Samir; Amri, F.; Saâd, Ali; Holterhus, Paul‐Martin; Gribaa, Moez

doi:10.1016/j.gene.2012.07.027

Cited by 11 publications

(15 citation statements)

References 40 publications

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“…The percentage of homozygous genotypes observed in the present study (46.7%) is higher than in the majority of the countries (Serbia 13% [38], China 16.1% [6], USA 21% [24], Tunisia 24% [30], the Netherlands 28.3% [39], Croatia 33% [12], Romania 33.3% [40], Brazil 39% [41]), even though not one case of consanguinity was reported. Alleles with multiple pathogenic variants accounted for 8.2% of unrelated alleles.…”

Section: Discussioncontrasting

confidence: 56%

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CYP21A2 Gene Pathogenic Variants: A Multicenter Study on Genotype–Phenotype Correlation from a Portuguese Pediatric Cohort

et al. 2019

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Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is an autosomal recessive disorder characterized by 3 overlapping phenotypes: salt-wasting (SW), simple virilizing (SV), and non-classic (NC). We aimed at conducting a nationwide genotype description of the CAH pediatric patients and to establish their genotype–phenotype correlation. Methods: CAH patients were recruited from Portuguese pediatric endocrinology centers and classified as SW, SV, or NC. Genetic analysis was performed by polymerase chain reaction (sequence specific primer, restriction fragment length polymorphism) or direct Sanger sequencing. Genotypes were categorized into 4 groups (0, A, B, and C), according to their predicted enzymatic activity. In each group, the expected phenotype was compared to the observed phenotype to assess the genotype–phenotype correlation. Results: Our cohort comprises 212 unrelated pediatric CAH patients (29% SW, 11% SV, 60% NC). The most common pathogenic variant was p.(Val282Leu; 41.3% of the 424 alleles analyzed). The p.(Val282Leu) variant, together with c.293-13A/C>G, p.(Ile173Asn), p.(Leu308Thr), p.(Gln319*), and large deletions/conversions were responsible for 86.4% of the mutated alleles. Patients’ stratification by disease subtype revealed that the most frequent pathogenic variants were c.293-13A/C>G in SW (31.1%), p.(Ile173Asn) in SV (46.9%), and p.(Val282Leu) in NC (69.5%). The most common genotype was homozygosity for p.(Val282Leu; 33.0%). Moreover, we found 2 novel variants: p.(Ile161Thr) and p.(Trp202Arg), in exons 4 and 5, respectively. The global genotype-phenotype correlation was 92.4%. Group B (associated with the SV form) showed the lowest genotype–phenotype correlation (80%). Conclusion: Our cohort has one of the largest NC CAH pediatric populations described. We emphasize the high frequency of the p.(Val282Leu) variant and the very high genotype–phenotype correlation observed.

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Section: Discussioncontrasting

confidence: 56%

“…In other populations, the p.(Val282Leu) pathogenic variant accounts for approximately 35–55% of NC CAH [11, 25, 30-35]. This high frequency is also found in Galicia (63.2%) [18], in the northwest of the Iberian Peninsula.…”

Section: Discussionmentioning

confidence: 98%

CYP21A2 Gene Pathogenic Variants: A Multicenter Study on Genotype–Phenotype Correlation from a Portuguese Pediatric Cohort

et al. 2019

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“…Similarly, 72% of a Tunisian cohort with CAH presented with ambiguous genitalia and or salt losing crisis. 6 This can be explained by the lack of newborn screening for CAH in this population. Universal neonatal screening for CAH aims at identification of affected infants and starting hormonal replacement therapy, thus preventing salt losing crisis and its consequences, including mental retardation, and death.…”

Section: Discussionmentioning

confidence: 95%

A CYP21A2 gene mutation in patients with congenital adrenal hyperplasia

Mohamed

El-Kholy

Al-Juryyan

et al. 2015

SMJ

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Objectives:The aim of this study is to determine congenital adrenal hyperplasia (CAH) with the pattern of CYP21A2 gene-mutations in Saudi children.Methods:Between January 2011 and March 2014 at King Fahad Military Complex, Dhahran, Saudi Arabia, we thoroughly examined 11 patients with CAH and 2 asymptomatic individuals with a history of affected siblings. Additionally, we sequenced the full coding regions of the CYP21A2 gene and screened the gene for deletion(s)/duplication(s) using the multiplex ligation-dependent probe amplification (MLPA) technique.Results:Nine patients had classic CAH and presented with ambiguous genitalia and/or salt losing crisis. Two patients had the non-classic form of CAH and presented with precocious puberty. The remaining 2 subjects were asymptomatic. Screening the CYP21A2 gene, we detected p.Gln318X mutation in 4 patients, c.290 -13 C>G (IVS2-13C>G) in another 4, and a common deletion, involving exons 6 and 8 in 3 patients.Conclusion:Our strategy of Sanger sequencing followed by MLPA was very successful in detecting CYP21A2 mutations in all patients with CAH.

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“…Different projects focused on different variants. For example, preimplantation genetic screen currently focused on CNV detection [25][26][27], inheritable diseases studies were mainly interested in SNP calling [28][29][30][31], and cancer-related studies might concern CNVs, SNPs, and other variants [32,33]. There was no best method for all projects, but there was always a more appropriate one for a certain project.…”

Section: Discussionmentioning

confidence: 99%

The comparison of the performance of four whole genome amplification kits on ion proton platform in copy number variation detection

Zhang

Liang

et al. 2017

Bioscience Reports

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Correspondence: Jichun Tan (tjczjh@163.com) and Caixia Liu (liucx1716@163.com) With the development and clinical application of genomics, more and more concern is focused on single-cell sequencing. In the process of single-cell sequencing, whole genome amplification is a key step to enrich sample DNA. Previous studies have compared the performance of different whole genome amplification (WGA) strategies on Illumina sequencing platforms, but there is no related research aimed at Ion Proton platform, which is also a popular next-generation sequencing platform. Here by amplifying cells from six cell lines with different karyotypes, we estimated the data features of four common commercial WGA kits (PicoPLEX WGA Kit, GenomePlex Single Cell Whole Genome Amplification Kit, MALBAC Single Cell Whole Genome Amplification Kit, and REPLI-g Single Cell Kit), including median absolute pairwise difference, uniformity, reproducibility, and fidelity, and examined their performance of copy number variation detection. The results showed that both MALBAC and PicoPLEX could yield high-quality data and had high reproducibility and fidelity; and as for uniformity, PicoPLEX was slightly superior to MALBAC.

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Steroid 21-hydroxylase gene mutational spectrum in 50 Tunisian patients: Characterization of three novel polymorphisms

Cited by 11 publications

References 40 publications

<b><i>CYP21A2</i></b> Gene Pathogenic Variants: A Multicenter Study on Genotype–Phenotype Correlation from a Portuguese Pediatric Cohort

<b><i>CYP21A2</i></b> Gene Pathogenic Variants: A Multicenter Study on Genotype–Phenotype Correlation from a Portuguese Pediatric Cohort

A CYP21A2 gene mutation in patients with congenital adrenal hyperplasia

The comparison of the performance of four whole genome amplification kits on ion proton platform in copy number variation detection

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