Navigating the Complex Landscape of CYP21A2  Variants

Dubey, Sudhisha; Gupta, Neerja

doi:10.1007/s12098-023-04951-9

Cited by 1 publication

(2 citation statements)

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“…Approximately 75% of the CYP21A2 pathogenic variants are transferred by conversion (microconversion when the event involves only one variant or large conversion when more pseudogene variants are involved) from the pseudogene during meiosis, while only 5-10% of pathogenic alleles harbor CYP21A2 variants that do not result in gene conversions [12][13][14][15][16]. In contrast, 20-25% of the cases of 21OHD are related to large misalignments due to unequal crossing over during meiosis.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, 20-25% of the cases of 21OHD are related to large misalignments due to unequal crossing over during meiosis. These events may cause gene deletion or amplification, and also broader deletions involving the CYP21A2 gene and the other contiguous genes [9,[14][15][16][17]. For example, the CYP21A1P/CYP21A2 chimeric gene is the result of a recombination between CYP21A1P and CYP21A2 genes as an unequal crossing over occurs during meiosis [18].…”

Section: Introductionmentioning

confidence: 99%

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Challenging Molecular Diagnosis of Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency: Case Series and Novel Variants of CYP21A2 Gene

Concolino

2024

CIMB

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Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive genetic defects in cortisol synthesis and shows elevated ACTH concentrations, which in turn has downstream effects. The most common variant of CAH, 21-hydroxylase deficiency (21OHD), is the result of pathogenic variants in the CYP21A2 gene and is one of the most common monogenic disorders. However, the genetics of 21OHD is complex and challenging. The CYP21A2 gene is located in the RCCX copy number variation (CNV), a complex, multiallelic, and tandem CNV in the major histocompatibility complex (MHC) class III region on chromosome 6 (band 6p21.3). Here, CYP21A2 and its pseudogene CYP21A1P are located 30 kb apart and share a high nucleotide homology of approximately 98% and 96% in exons and introns, respectively. This high-sequence homology facilitates large structural rearrangements, copy number changes, and gene conversion through intergenic recombination. There is a good genotype–phenotype correlation in 21OHD, and genotyping can be performed to confirm the clinical diagnosis, predict long-term outcomes, and determine genetic counseling. Thus, genotyping in CAH is clinically relevant but the interpretations can be challenging for non-initiated clinicians. Here, there are some concrete examples of how molecular diagnosis can sometimes require the use of multiple molecular strategies.

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Section: Introductionmentioning

confidence: 99%