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| Genomic newborn screening: ICoNS v0.27 | CYP21A2 |
Thomas Minten changed review comment from: On RUSP website CYP21A2 specifically mentioned as causative gene ClinGen: haploinsufficiency score of 30, high level of evidence Prevalence SW-CAH and SV-CAH: 1:11,000-1:14,000 Disease pathway: enzyme 21-hydroxylase produces cortisol and aldosterone -> important for hormone balance Presentation in neonatal onset, childhood: poor feeding, vomiting, weight loss or failure to thrive, excessive sleepiness or lethargy, irritability, and diarrhea. In females, ambiguous genitalia Treatment: Lifelong glucocorticoid replacement therapy (such as hydrocortisone) Inheritance: biallelic (recessive), autosomal or pseudoautosomal Current screening method for CAH: First tier: 17‑hydroxyprogesterone (17‑OHP) Second tier: steroid profiling/CYP21A2 genotyping Included (in 2024) in 16/27 gNBS programs, ranks 130 out of 4390 Included in BabyDetect, BabyScreen+,Generation, Beginnings, Puglia, Screen4Care, Nurture,… Not in Guardian, EarlyCheck Chen et al and several commercial panels Problem: Standard WGS methodologies face challenges in accurately detecting CYP21A2 variants because of this homology and population complexity. Therefore, by most programs is only used in conjunction with 17-OHP levels. Sources: Other; to: Gene causes adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency ClinGen: haploinsufficiency score of 30, high level of evidence Prevalence SW-CAH and SV-CAH: 1:11,000-1:14,000 Disease pathway: gene important for production of enzyme 21-hydroxylase, which in turn produces cortisol and aldosterone which is important for hormone balance Presentation in neonatal onset, childhood: poor feeding, vomiting, weight loss or failure to thrive, excessive sleepiness or lethargy, irritability, and diarrhea. In females, ambiguous genitalia. Treatment: Lifelong glucocorticoid replacement therapy (such as hydrocortisone) Inheritance: biallelic (recessive), autosomal or pseudoautosomal Current biochemical screening method for CAH is performed in most countries: First tier: 17‑hydroxyprogesterone (17‑OHP) Second tier: steroid profiling/CYP21A2 genotyping High genotype phenotype correlation as discussed in PMID 23359698 Included (in 2024) in 16/27 gNBS programs, ranks 130 out of 4390 Included in BabyDetect, BabyScreen+,Generation, Beginnings, Puglia, Screen4Care, Nurture,… Not in Guardian, EarlyCheck, Chen et al. and several commercial panels Problem: Standard WGS methodologies face challenges in accurately detecting CYP21A2 variants because of homology and population complexity. Therefore, by most gNBS programs the results in this gene are only used in conjunction with 17-OHP levels. Sources: Other |
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| Genomic newborn screening: ICoNS v0.27 | CYP21A2 |
Thomas Minten gene: CYP21A2 was added gene: CYP21A2 was added to Genomic newborn screening: ICoNS. Sources: Other Mode of inheritance for gene: CYP21A2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: CYP21A2 were set to CYP21A2 Adrenal hyperplasia, congenital, due to 21-hydroxylase deficiency Mode of pathogenicity for gene: CYP21A2 was set to Other Review for gene: CYP21A2 was set to GREEN Added comment: On RUSP website CYP21A2 specifically mentioned as causative gene ClinGen: haploinsufficiency score of 30, high level of evidence Prevalence SW-CAH and SV-CAH: 1:11,000-1:14,000 Disease pathway: enzyme 21-hydroxylase produces cortisol and aldosterone -> important for hormone balance Presentation in neonatal onset, childhood: poor feeding, vomiting, weight loss or failure to thrive, excessive sleepiness or lethargy, irritability, and diarrhea. In females, ambiguous genitalia Treatment: Lifelong glucocorticoid replacement therapy (such as hydrocortisone) Inheritance: biallelic (recessive), autosomal or pseudoautosomal Current screening method for CAH: First tier: 17‑hydroxyprogesterone (17‑OHP) Second tier: steroid profiling/CYP21A2 genotyping Included (in 2024) in 16/27 gNBS programs, ranks 130 out of 4390 Included in BabyDetect, BabyScreen+,Generation, Beginnings, Puglia, Screen4Care, Nurture,… Not in Guardian, EarlyCheck Chen et al and several commercial panels Problem: Standard WGS methodologies face challenges in accurately detecting CYP21A2 variants because of this homology and population complexity. Therefore, by most programs is only used in conjunction with 17-OHP levels. Sources: Other |
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