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

• Published in: BMC research notes Vol. 12; no. 1; pp. 711 - 6
• Main Authors: Kolli, Vipula, Kim, Hannah, Rao, Hamsini, Lao, Qizong, Gaynor, Alison, Milner, Joshua D., Merke, Deborah P.
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.10.2019; BioMed Central; BMC
• Subjects: Adolescent; Adrenal Hyperplasia, Congenital - blood; Adrenal Hyperplasia, Congenital - genetics; Adult; Aged; Antibodies; Biomarkers - blood; Child; Child, Preschool; Collagen; Complications and side effects; Congenital adrenal hyperplasia; Connective Tissue Diseases - diagnosis; CYP21A2; Cytochrome P-450; Demographic aspects; Diagnosis; Ehlers-Danlos syndrome; Ehlers-Danlos Syndrome - blood; Ehlers-Danlos Syndrome - genetics; Epigenetic inheritance; Female; Gene Deletion; Genes; Genetic disorders; Glycoproteins; Health aspects; Hernia; Humans; Hyperplasia; Joint Instability - diagnosis; Male; Measurement; Middle Aged; Mutation; Organizations; Phenotype; Research Note; Risk factors; Steroid 21-Hydroxylase - genetics; Tenascin - blood; Tenascin - genetics; Tenascin-X; TNXB; Young Adult; United States; Ehlers–Danlos syndrome; TNXB; Congenital adrenal hyperplasia; Tenascin-X; CYP21A2
• ISSN: 1756-0500; 1756-0500
• DOI: 10.1186/s13104-019-4753-7

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. 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.