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Chimeric Genes Causing 11β-Hydroxylase Deficiency: Implications in Clinical and Molecular Diagnosis.

Authors :
Concolino, Paola
Source :
Molecular Diagnosis & Therapy. Mar2024, Vol. 28 Issue 2, p215-224. 10p.
Publication Year :
2024

Abstract

Deficiency of 11β-hydroxylase (11β-OHD) is the second most common cause of congenital adrenal hyperplasia (CAH), accounting for 0.2–8% of all cases. The disease is transmitted as an autosomal recessive trait and the underlying genetic causes of 11β-OHD are primarily small pathogenic variants affecting the CYP11B1 gene coding the 11β-hydroxylase enzyme. However, special events complicate the molecular diagnosis of 11β-OHD such as an unequal crossing over between the CYP11B2 (coding aldosterone synthase enzyme) and CYP11B1 genes. The resulting allele contains a hybrid gene, with a CYP11B2 5′-end and a CYP11B1 3′-end, where the CYP11B1 gene is under the control of the CYP11B2 promoter and thus not responding to the adrenocorticotropin (ACTH) but to angiotensin II and K+. This leads a reduction of cortisol production in 11β-OHD. In particular, CYP11B2/CYP11B1 chimeric genes can be distinguished into two groups depending on the breakpoint site: chimeras with breakpoint after the exon 5 of CYP11B2 preserve the aldosterone synthase activity, the others with breakpoint before exon 5 lose this function. In the last case, a more severe phenotype is expected. The aim of this review was to explore the setting of CYP11B2/CYP11B1 chimeras in 11β-OHD, performing a careful review of clinical literature cases. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
11771062
Volume :
28
Issue :
2
Database :
Academic Search Index
Journal :
Molecular Diagnosis & Therapy
Publication Type :
Academic Journal
Accession number :
175966489
Full Text :
https://doi.org/10.1007/s40291-024-00697-y