Mutation in TNXB gene causes moderate to severe Ehlers-Danlos syndrome

Abstract

We report a 28-year-old female who presented with severe joint pain, chronic muscle weakness, Raynaud’s phenomenon, and hypermobility. She was found to have a 6074A > T nucleotide transition in the TNXB gene causing an amino acid protein change at Asp2025Val classified as likely pathogenic. We add this clinical report to the literature and classical human disease gene catalogs to identify this specific mutation as disease-causing. This gene variant was reported previously in a different 36-year-old patient who shared our patient’s symptoms of joint hypermobility, skeletal and joint pain, skin elasticity and musculoskeletal problems, thereby causing a more severe presentation than seen in the hypermobility type of Ehlers-Danlos syndrome (EDS). At the time of writing, a few mutations in the TNXB gene have been recognized as pathogenic causing EDS due to tenascin-X deficiency, but the variant identified in our patient has not been recognized as pathogenic in online genetic databases. Our case study in combination with peer-reviewed literature suggests that the 6074A > T nucleotide transition in the TNXB gene may be classified as disease-causing for EDS due to tenascin-X deficiency.

Keywords: Ehlers-Danlos syndrome; Genetic variants; Mutations; Hypermobility; Joint pain; Muscle weakness; Raynaud’s phenomenon; Tenascin-X; TNXB; Ehlers-Danlos syndrome due to tenascin-X deficiency

Core tip: Various types of Ehlers-Danlos syndrome (EDS) have unique phenotypic features and genetic causes that are under investigation. This case report presents a gene variant (6074A > T nucleotide transition in the TNXB gene) not previously classified as disease-causing which we propose should be classified as pathogenic. This variant appears to produce joint hypermobility, skeletal pain, and musculoskeletal problems and should be classified as causing EDS due to tenascin-X deficiency.