title: Mutation inTNXBgene 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 theTNXBgene 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 theTNXBgene 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 theTNXBgene may be classified as disease-causing for EDS due to tenascin-X deficiency.
authors.affiliation: Department of Psychiatry, Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Carolyn S
authors.initials: CS
authors.lastname: Kaufman
authors.affiliation: Department of Psychiatry, Behavioral Sciences and Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Merlin G
authors.initials: MG
authors.lastname: Butler
keywords: Ehlers-Danlos syndrome; Ehlers-Danlos syndrome due to tenascin-X deficiency; Genetic variants; Hypermobility; Joint pain; Muscle weakness; Mutations; Raynaud’s phenomenon; TNXB; Tenascin-X