Recurrent pneumothorax in a case of tenascin‐X deficient Ehlers–Danlos syndrome: Broadening the phenotypic spectrum. Issue 5 (6th February 2022)

• Record Type: Journal Article
• Authors: Santoreneos, Renee; Vakulin, Cassandra; Ellul, Melissa; Rawlings, Lesley; Hardy, Tristan; Poplawski, Nicola
• Is Part Of: American journal of medical genetics. Volume 188:Issue 5(2022)
• Page Start: 1583
• Page End: 1588
• Publication Date: 2022-02-06
• Subjects: classical‐like Ehlers–Danlos syndrome -- Ehlers–Danlos syndrome -- pneumothorax -- tenascin‐X deficiency; Medical genetics -- Periodicals; 616.14205
• DOI: 10.1002/ajmg.a.62674
• Languages: English
• ISSNs: 1552-4825

Abstract

Abstract: The genomic region surrounding the Tenascin‐XB gene ( TNXB ) is a complex and duplicated region, with several pseudogenes that predispose to high rates of homologous recombination. Classical‐like Ehlers–Danlos syndrome (clEDS) is the result of tenascin‐X deficiency due to biallelic loss of function variants in the TNXB gene. Here we present a patient with clEDS and spontaneous pneumothorax, a feature not previously reported to be associated with this condition. Two inherited pathogenic/likely pathogenic variants were identified; a previously reported deletion resulting in a TNXA/TNXB chimeric gene and a novel frameshift variant. The Tenascin‐XB gene is well described in the literature to be associated with collagen metabolism, stabilization of the fibrillar‐collagen matrix and is expressed abundantly in the extracellular matrix. We propose that tenascin‐X deficiency is directly related to pneumothorax predisposition. This case expands the phenotypic spectrum of clEDS and highlights the challenges with molecular analysis and diagnosis