Dataset Information

Congenital adrenal hyperplasia due to two rare CYP21A2 variant alleles, including a novel attenuated CYP21A1P/CYP21A2 chimera.

ABSTRACT:

Background

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21OH) deficiency is an autosomal recessive inborn error of cortisol biosynthesis, with varying degrees of aldosterone production. There is a continuum of phenotypes which generally correlate with genotype and the expected residual 21OH activity of the less severely impaired allele. CYP21A1P/CYP21A2 chimeric genes caused by recombination between CYP21A2 and its highly homologous CYP21A1P pseudogene are common in CAH and typically associated with salt-wasting CAH, the most severe form. Nine chimeras have been described (CH-1 to CH-9).

Aims

The aim of this study was to genetically evaluate two variant alleles carried by a 22-year-old female with the non-salt-wasting simple virilizing form of CAH and biallelic 30-kb deletions.

Methods

The haplotypes of the CYP21A2 heterozygous variants, as well as the chimeric junction sites, were determined by Sanger sequencing TA clones of an allele-specific PCR product.

Results

Genetic testing revealed two rare CYP21A1P/CYP21A2 chimeras: allele 1 matches the previously described CAH CH-1 chimera but without the P30L variant, and allele 2, termed here as novel CAH CH-10, has a junction site between c.293-37 and c.29314, which is expected to retain partial 21OH activity.

Conclusion

These two variant alleles further document the complex nature of RCCX modules and highlight that not all CYP21A1P/CYP21A2 chimera severely impair 21OH activity.

SUBMITTER: Lao Q

PROVIDER: S-EPMC10337281 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

Congenital adrenal hyperplasia due to two rare CYP21A2 variant alleles, including a novel attenuated CYP21A1P/CYP21A2 chimera.

Lao Qizong Q Burkardt Deepika D DD Kollender Sarah S Faucz Fabio R FR Merke Deborah P DP

Molecular genetics & genomic medicine 20230508 7

<h4>Background</h4>Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase (21OH) deficiency is an autosomal recessive inborn error of cortisol biosynthesis, with varying degrees of aldosterone production. There is a continuum of phenotypes which generally correlate with genotype and the expected residual 21OH activity of the less severely impaired allele. CYP21A1P/CYP21A2 chimeric genes caused by recombination between CYP21A2 and its highly homologous CYP21A1P pseudogene are common in CAH an ...[more]

PMID: 37157918

Similar Datasets

Project description:ObjectiveTo raise awareness of Cytochrome P450 Oxidoreductase Deficiency (PORD, a rare form of congenital adrenal hyperplasia (CAH), through a case of pregnant woman with virilization symptoms.Case descriptionA 30-year-old Chinese woman was referred to hospital after 7 years of presenting signs of virilization, including voice deepening, acromegaly, hirsutism, clitoromegaly, and acne. These symptoms appeared since her third gestation. Her second birth died 9 hours after birth and had signs of clitoris hypertrophy. Her third born was a son who presented with flat nose, radius and humerus bone malformation, and small penis at birth. Panel of POR-related genetic tests revealed that the patient carried c.1370 G>A (p.R457H), which is a POR heterozygous gene, while her husband carried a POR heterozygous gene as well, c.1379 C>A (p.S460Y). Two heterozygous mutations of the POR were found in her son: c.1370 G>A and c.1379 C>A. In PORD, c.1370 G>A (p.R457H) was reported as a susceptible gene, while c.1379 C>A (p.S460Y) has not been reported as responsible for the disease so far.Discussion and literature reviewPORD is a rare form of CAH and caused by POR gene mutations. Most PORD patients are identified and diagnosed in pediatrics department. Internal medicine and obstetrics physicians are unfamiliar with the disease. As clinical manifestations are diverse, PORD could be easy to miss or to be misdiagnosed. Typical clinical manifestation includes adrenal insufficiency-related symptoms, such as bone malformations and sexual development disorders. PORD is diagnosed through genetic testing. Investigations of steroid metabolic products in urine through gas chromatography-mass spectrometry or liquid chromatography-mass spectrometry are also helpful for the diagnosis, but neither of them are widely available in China. In this case, the patient had a history of infertility, and her third child was born with congenital defect and carried a PORD-related gene. In general clinical practice, if a pregnant woman presents with abnormal virilization symptoms, CAH possibilities should be considered, including rare causes such as PORD.ConclusionPORD is a rare autosomal recessive genetic disease. We summarised the clinical characteristics and genotypes that were previously reported in the Chinese population and identified a novel mutation.

Dataset Information

Congenital adrenal hyperplasia due to two rare CYP21A2 variant alleles, including a novel attenuated CYP21A1P/CYP21A2 chimera.

Background

Aims

Methods

Results

Conclusion

Publications

Congenital adrenal hyperplasia due to two rare CYP21A2 variant alleles, including a novel attenuated CYP21A1P/CYP21A2 chimera.

Similar Datasets

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