High-Throughput Screening for CYP21A1P-TNXA/TNXB Chimeric Genes Responsible for Ehlers Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia

Many patients with congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency have CAH-X syndrome, a connective tissue dysplasia consistent with hypermobility type Ehlers Danlos syndrome due to a contiguous gene deletion involving the adjacent CYP21A2 and TNXB genes. CAH-X syndrome is caused by carrying CYP21A1P-TNXA/TNXB chimeric genes (CAH-X CH-1 and CH-2) on one or more alleles. Genetic analysis is cumbersome due to pseudogene interference. We developed a PCR-based CAH-X high-throughput screening method to assess the copy numbers of TNXB exons 35 and 40 that is amenable to either quantitative PCR or droplet digital PCR.
Source: Journal of Molecular Diagnostics - Category: Pathology Authors: Tags: Regular Article Source Type: research

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Journal Name: Journal of Pediatric Endocrinology and Metabolism Issue: Ahead of print
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Superti-Furga Garavelli Variations in genes encoding for the enzymes responsible for synthesizing the linker region of proteoglycans may result in recessive conditions known as “linkeropathies”. The two phenotypes related to mutations in genes B4GALT7 and B3GALT6 (encoding for galactosyltransferase I and II respectively) are similar, characterized by short stature, hypotonia, joint hypermobility, skeletal features and a suggestive face with prominent forehead, thin soft tissue and prominent eyes. The most outstanding feature of these disorders is the combination of severe connective tissue in...
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Source: Journal of Pediatric Urology - Category: Urology & Nephrology Authors: Source Type: research
Publication date: Available online 21 June 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Qizong Lao, Brittany Brookner, Deborah P. MerkeMany patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have CAH-X syndrome, a connective tissue dysplasia consistent with hypermobility-type Ehlers-Danlos syndrome due to a contiguous gene deletion involving the adjacent CYP21A2 and TNXB genes. CAH-X syndrome is caused by carrying CYP21A1P-TNXA/TNXB chimeric genes (CAH-X CH-1 and CH-2) on one or more alleles. Genetic analysis is cumbersome due to pseudogene interference. We developed a PCR-bas...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research
Publication date: Available online 21 June 2019Source: The Journal of Molecular DiagnosticsAuthor(s): Qizong Lao, Brittany Brookner, Deborah P. MerkeMany patients with congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency have CAH-X syndrome, a connective tissue dysplasia consistent with hypermobility type Ehlers Danlos syndrome due to a contiguous gene deletion involving the adjacent CYP21A2 and TNXB genes. CAH-X syndrome is caused by carrying CYP21A1P-TNXA/TNXB chimeric genes (CAH-X CH-1 and CH-2) on one or more alleles. Genetic analysis is cumbersome due to pseudogene interference. We developed a PCR-bas...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research
Many patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency have CAH-X syndrome, a connective tissue dysplasia consistent with hypermobility-type Ehlers-Danlos syndrome due to a contiguous gene deletion involving the adjacent CYP21A2 and TNXB genes. CAH-X syndrome is caused by carrying CYP21A1P-TNXA/TNXB chimeric genes (CAH-X CH-1 and CH-2) on one or more alleles. Genetic analysis is cumbersome due to pseudogene interference. We developed a PCR-based CAH-X high-throughput screening method to assess the copy numbers of TNXB exons 35 and 40; this method is amenable to either real-time quantitativ...
Source: Journal of Molecular Diagnostics - Category: Pathology Authors: Tags: Regular article Source Type: research
Mutations of theCYP21A2 gene encoding adrenal 21-hydroxylase cause congenital adrenal hyperplasia (CAH). TheCYP21A2 gene is partially overlapped by theTNXB gene, which encodes an extracellular matrix protein called Tenascin-X (TNX). Mutations affecting both alleles ofTNXB cause a severe, autosomal recessive form of Ehlers-Danlos syndrome (EDS). Rarely, patients with severe, salt-wasting CAH have deletions ofCYP21A2 that extend intoTNXB, resulting in a “contiguous gene syndrome” consisting of CAH and EDS. Heterozygosity forTNXB mutations causing haploinsufficiency of TNX may be associated with the mild “hy...
Source: Hormone Research in Paediatrics - Category: Endocrinology Source Type: research
We present here three patients with biallelic CAH‐X and identify a novel dominant‐negative chimera termed CAH‐X CH‐3. Compared with monoallelic CAH‐X, biallelic CAH‐X results in a more severe phenotype with skin features characteristic of classical EDS. We present evidence for disrupted tenascin‐X function and computational data linking the type of TNXB variant to disease severity. Biallelic TNXB variants in patients with congenital adrenal hyperplasia due to CYP21A2 deletions result in a classical Ehlers‐Danlos syndrome phenotype with skin hyperextensibility, widened atrophic scars and joint hypermobility...
Source: Human Mutation - Category: Genetics & Stem Cells Authors: Tags: Brief Report Source Type: research
More News: Congenital Adrenal Hyperplasia | Ehlers-Danlos Syndrome | Genetics | Pathology