title: Compound heterozygous mutations of the TNXB gene cause primary myopathy.
abstract: Complete deficiency of the extracellular matrix glycoprotein tenascin-X (TNX) leads to recessive forms of Ehlers-Danlos syndrome, clinically characterized by hyperextensible skin, easy bruising and joint hypermobility. Clinical and pathological studies, immunoassay, and molecular analyses were combined to study a patient suffering from progressive muscle weakness. Clinical features included axial and proximal limb muscle weakness, subclinical heart involvement, minimal skin hyperextensibility, no joint abnormalities, and a history of easy bruising. Skeletal muscle biopsy disclosed striking muscle consistency and the abnormal presence of myotendinous junctions in the muscle belly. TNX immunostaining was markedly reduced in muscle and skin, and serum TNX levels were undetectable. Compound heterozygous mutations were identified: a previously reported 30kb deletion and a non-synonymous novel missense mutation in the TNXB gene. This study identifies a TNX-deficient patient presenting with a primary muscle disorder, thus expanding the phenotypic spectrum of TNX-related abnormalities. Biopsy findings provide evidence that TNX deficiency leads to muscle softness and to mislocalization of myotendinous junctions.
authors.affiliation: Centre de référence des Maladies Neuromusculaires, Département de Neurologie, Centre Hospitalier Universitaire d'Angers, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Pénisson-Besnier
authors.forename: Valérie
authors.initials: V
authors.lastname: Allamand
authors.forename: Philippe
authors.initials: P
authors.lastname: Beurrier
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Joost
authors.initials: J
authors.lastname: Schalkwijk
authors.forename: Ivonne
authors.initials: I
authors.lastname: van Vlijmen-Willems
authors.forename: Corine
authors.initials: C
authors.lastname: Gartioux
authors.forename: Fransiska
authors.initials: F
authors.lastname: Malfait
authors.forename: Delfien
authors.initials: D
authors.lastname: Syx
authors.forename: Laurent
authors.initials: L
authors.lastname: Macchi
authors.forename: Pascale
authors.initials: P
authors.lastname: Marcorelles
authors.forename: Brigitte
authors.initials: B
authors.lastname: Arbeille
authors.forename: Anne
authors.initials: A
authors.lastname: Croué
authors.forename: Anne
authors.initials: A
authors.lastname: De Paepe
authors.forename: Frédéric
authors.initials: F
authors.lastname: Dubas
mesh_terms: D000328:Adult; D004252:DNA Mutational Analysis; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging / Q000473:pathology / Q000648:ultrastructure; D009135:Muscular Diseases / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D019063:Tenascin / Q000235:genetics* / Q000378:metabolism; D014057:Tomography, X-Ray Computed
chemical_list: D019063:Tenascin; C081865:tenascin X
keywords: Connective tissue disorders; Ehlers–Danlos syndrome; Extracellular matrix; Myopathy; Tenascin-X