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Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X

OBJECTIVE: Approximately 10% of patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency carry a mutation that disrupts CYP21A2 and the flanking TNXB gene resulting in CAH-X, a contiguous gene deletion syndrome. TNXB encodes tenascin-X (TNX), an extracellular matrix glycop...

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Autores principales: Kolli, Vipula, Kim, Hannah, Rao, Hamsini, Lao, Qizong, Gaynor, Alison, Milner, Joshua D., Merke, Deborah P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820911/
https://www.ncbi.nlm.nih.gov/pubmed/31666125
http://dx.doi.org/10.1186/s13104-019-4753-7
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author Kolli, Vipula
Kim, Hannah
Rao, Hamsini
Lao, Qizong
Gaynor, Alison
Milner, Joshua D.
Merke, Deborah P.
author_facet Kolli, Vipula
Kim, Hannah
Rao, Hamsini
Lao, Qizong
Gaynor, Alison
Milner, Joshua D.
Merke, Deborah P.
author_sort Kolli, Vipula
collection PubMed
description OBJECTIVE: Approximately 10% of patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency carry a mutation that disrupts CYP21A2 and the flanking TNXB gene resulting in CAH-X, a contiguous gene deletion syndrome. TNXB encodes tenascin-X (TNX), an extracellular matrix glycoprotein that plays an important role in collagen organization. TNXB impairment is associated with Ehlers–Danlos syndrome. Symptoms include joint hypermobility, hernias and cardiac defects. We measured serum TNX using an antibody targeting the amino-terminal of the TNX protein in 161 subjects, including extensively genotyped and phenotyped CAH patients, their relatives, and healthy controls. RESULTS: We evaluated the potential of serum TNX as a screening tool for CAH-X. CAH-X patients, especially haploinsufficient patients carrying the TNXA-TNXB chimeric gene CAH-X-CH-1 showed reduced TNX levels compared to controls (P < 0.05). TNX levels were similar in all subjects carrying a TNXB mutation. However, CAH patients who did not harbor a TNXB mutation also had reduced TNX compared to controls (P < 0.001). Thus, measuring serum TNX is not an effective screen for CAH-X amongst patients with CAH. TNXB genotyping is recommended for CAH patients who have symptoms of a connective tissue disorder. Epigenetic factors that influence TNX expression require further study.
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spelling pubmed-68209112019-11-04 Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X Kolli, Vipula Kim, Hannah Rao, Hamsini Lao, Qizong Gaynor, Alison Milner, Joshua D. Merke, Deborah P. BMC Res Notes Research Note OBJECTIVE: Approximately 10% of patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency carry a mutation that disrupts CYP21A2 and the flanking TNXB gene resulting in CAH-X, a contiguous gene deletion syndrome. TNXB encodes tenascin-X (TNX), an extracellular matrix glycoprotein that plays an important role in collagen organization. TNXB impairment is associated with Ehlers–Danlos syndrome. Symptoms include joint hypermobility, hernias and cardiac defects. We measured serum TNX using an antibody targeting the amino-terminal of the TNX protein in 161 subjects, including extensively genotyped and phenotyped CAH patients, their relatives, and healthy controls. RESULTS: We evaluated the potential of serum TNX as a screening tool for CAH-X. CAH-X patients, especially haploinsufficient patients carrying the TNXA-TNXB chimeric gene CAH-X-CH-1 showed reduced TNX levels compared to controls (P < 0.05). TNX levels were similar in all subjects carrying a TNXB mutation. However, CAH patients who did not harbor a TNXB mutation also had reduced TNX compared to controls (P < 0.001). Thus, measuring serum TNX is not an effective screen for CAH-X amongst patients with CAH. TNXB genotyping is recommended for CAH patients who have symptoms of a connective tissue disorder. Epigenetic factors that influence TNX expression require further study. BioMed Central 2019-10-30 /pmc/articles/PMC6820911/ /pubmed/31666125 http://dx.doi.org/10.1186/s13104-019-4753-7 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Note
Kolli, Vipula
Kim, Hannah
Rao, Hamsini
Lao, Qizong
Gaynor, Alison
Milner, Joshua D.
Merke, Deborah P.
Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X
title Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X
title_full Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X
title_fullStr Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X
title_full_unstemmed Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X
title_short Measurement of serum tenascin-X in patients with congenital adrenal hyperplasia at risk for Ehlers–Danlos contiguous gene deletion syndrome CAH-X
title_sort measurement of serum tenascin-x in patients with congenital adrenal hyperplasia at risk for ehlers–danlos contiguous gene deletion syndrome cah-x
topic Research Note
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820911/
https://www.ncbi.nlm.nih.gov/pubmed/31666125
http://dx.doi.org/10.1186/s13104-019-4753-7
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