Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency

Version 1 : Received: 23 June 2022 / Approved: 24 June 2022 / Online: 24 June 2022 (04:09:50 CEST)

How to cite: Paragliola, R.M.; Perrucci, A.; Foca, L.; Urbani, A.; Concolino, P. Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency. Preprints 2022, 2022060329. https://doi.org/10.20944/preprints202206.0329.v1 Paragliola, R.M.; Perrucci, A.; Foca, L.; Urbani, A.; Concolino, P. Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency. Preprints 2022, 2022060329. https://doi.org/10.20944/preprints202206.0329.v1

Abstract

21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3’untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30-kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers Danlos Syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population.

Keywords

congenital adrenal hyperplasia; Ehlers Danlos Syndrome; CAH-X syndrome

Subject

Biology and Life Sciences, Anatomy and Physiology

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0


×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.