Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency
21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in <i>CYP21A2</i> gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The <i>CYP21A2</...
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MDPI AG
2022-07-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/11/13/3818 |
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| author | Rosa Maria Paragliola Alessia Perrucci Laura Foca Andrea Urbani Paola Concolino |
| author_facet | Rosa Maria Paragliola Alessia Perrucci Laura Foca Andrea Urbani Paola Concolino |
| author_sort | Rosa Maria Paragliola |
| collection | DOAJ |
| description | 21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in <i>CYP21A2</i> gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The <i>CYP21A2</i> 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 <i>CYP21A2</i> exon 10 overlap the last exon of <i>TNXB</i> 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 <i>TNXB</i> and its pseudogene <i>TNXA</i> causes a 30 kb deletion producing a chimeric <i>TNXA/TNXB</i> gene (CAH-X chimera) where both <i>CYP21A2</i> and <i>TNXB</i> 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 <i>CYP21A2</i> and part of the <i>TNXB</i> 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. |
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| language | English |
| last_indexed | 2024-03-09T04:04:36Z |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-706ddde6247c4138ac1fd2bb15178d952023-12-03T14:08:33ZengMDPI AGJournal of Clinical Medicine2077-03832022-07-011113381810.3390/jcm11133818Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase DeficiencyRosa Maria Paragliola0Alessia Perrucci1Laura Foca2Andrea Urbani3Paola Concolino4Unit of Endocrinology, Agostino Gemelli Foundation University Hospital IRCCS, 00168 Rome, ItalyClinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Agostino Gemelli Foundation University Hospital IRCCS, 00168 Rome, ItalyClinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Agostino Gemelli Foundation University Hospital IRCCS, 00168 Rome, ItalyClinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Agostino Gemelli Foundation University Hospital IRCCS, 00168 Rome, ItalyClinical Chemistry, Biochemistry and Molecular Biology Operations (UOC), Agostino Gemelli Foundation University Hospital IRCCS, 00168 Rome, Italy21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in <i>CYP21A2</i> gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The <i>CYP21A2</i> 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 <i>CYP21A2</i> exon 10 overlap the last exon of <i>TNXB</i> 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 <i>TNXB</i> and its pseudogene <i>TNXA</i> causes a 30 kb deletion producing a chimeric <i>TNXA/TNXB</i> gene (CAH-X chimera) where both <i>CYP21A2</i> and <i>TNXB</i> 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 <i>CYP21A2</i> and part of the <i>TNXB</i> 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.https://www.mdpi.com/2077-0383/11/13/3818congenital adrenal hyperplasiaEhlers–Danlos syndromeCAH-X syndrome |
| spellingShingle | Rosa Maria Paragliola Alessia Perrucci Laura Foca Andrea Urbani Paola Concolino Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency Journal of Clinical Medicine congenital adrenal hyperplasia Ehlers–Danlos syndrome CAH-X syndrome |
| title | Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency |
| title_full | Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency |
| title_fullStr | Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency |
| title_full_unstemmed | Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency |
| title_short | Prevalence of CAH-X Syndrome in Italian Patients with Congenital Adrenal Hyperplasia (CAH) Due to 21-Hydroxylase Deficiency |
| title_sort | prevalence of cah x syndrome in italian patients with congenital adrenal hyperplasia cah due to 21 hydroxylase deficiency |
| topic | congenital adrenal hyperplasia Ehlers–Danlos syndrome CAH-X syndrome |
| url | https://www.mdpi.com/2077-0383/11/13/3818 |
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