EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency

@article{BaumgartnerParzer2020EMQNBP,
  title={EMQN best practice guidelines for molecular genetic testing and reporting of 21-hydroxylase deficiency},
  author={Sabina Baumgartner-Parzer and Martina Witsch-Baumgartner and Wolfgang Hoeppner},
  journal={European Journal of Human Genetics},
  year={2020},
  volume={28},
  pages={1341 - 1367}
}
Molecular genetic testing for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is offered worldwide and is of importance for differential diagnosis, carrier detection and adequate genetic counseling, particularly for family planning. In 2008 the European Molecular Genetics Quality Network (EMQN) for the first time offered a European-wide external quality assessment scheme for CAH (due to 21-OH deficiency). The interest was great and over the last years at about 60… 
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19 Citations

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Molecular Diagnosis of Steroid 21-Hydroxylase Deficiency: A Practical Approach
TLDR
DNA testing of CYP21A2 constitutes an irreplaceable tool to detect severe alleles not just in family members of classical forms but also in mild late-onset forms of the disease and couples, and is also helpful in areas such as assisted reproduction and preimplantation diagnosis.
Allele-specific PCR and next generation sequencing based genetic screening for Congenital Adrenal Hyperplasia in India.
CYP21A2 mutations in pediatric patients with congenital adrenal hyperplasia in Costa Rica
Comprehensive Genetic Testing of CYP21A2: A Retrospective Analysis in Patients with Suspected Congenital Adrenal Hyperplasia
TLDR
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.
Neonatal Screening and Genotype-Phenotype Correlation of 21-Hydroxylase Deficiency in the Chinese Population
TLDR
It is suggested that neonatal screening effectively leads to the early diagnosis of 21-OHD and reduces fatal adrenal crisis.
Genotypic spectrum of 21-hydroxylase deficiency in an endogamous population
TLDR
Molecular characterization should be considered along with clinical and biochemical diagnosis of CAH since it could confirm the diagnosis, outline the treatment strategy and morbidity, and ensure proper genetic counseling.
Challenges of CYP21A2 genotyping in children with 21-hydroxylase deficiency: determination of genotype–phenotype correlation using next generation sequencing in Southeastern Anatolia
TLDR
This study revealed that the concordance rates of the severe genotypes with their phenotypes were good, while those of the milder genotypes were poor, which could have resulted from the complex characteristics of 21-OHD genotyping and the limitations of using NGS alone without integrating with other comprehensive methods.
Molecular Analysis of 21-Hydroxylase Deficiency Reveals Two Novel Severe Genotypes in Affected Newborns.
TLDR
A detailed molecular investigation of 13 newborns affected from the severe form of congenital adrenal hyperplasia related to 21-hydroxylase deficiency led to the identification of two novel frameshift CYP21A2 pathogenic variants related to the salt-wasting form of conjoined twins.
Meta Analysis of Variant Predictions in Congenital Adrenal Hyperplasia Caused by Mutations in CYP21A2
TLDR
Four predictors of CYP21A2 pathogenicity with good performance are identified, and these results can be used for future analysis to infer the impact of uncharacterized SNVs' in CYP 21A2.
Diagnostic Challenges in Nonclassical Congenital Adrenal Hyperplasia
TLDR
Current challenges in the diagnosis of nonclassical 21-hydroxylase deficiency (21-OHd), including the reasons that justify screening for this disorder, the clinical situations in which such screening is required, recent advances in the methods used in different settings, and the consequences that might arise from a diagnosis of 21- OHd NCAH are reviewed.
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