<i>TNXB</i>-related classical-like Ehlers-Danlos syndrome (<i>TNXB</i>-clEDS) is an ultrarare type of Ehlers-Danlos syndrome due to biallelic <i>null</i> variants in <i>TNXB</i>, encoding tenascin-X.
Tenascin-X is important for the proper deposition of collagen fibers in dermis and patients with a tenascin-X deficiency suffer from Ehlers Danlos syndrome.
Tenascin X (TNX) deficiency is a rare type of EDS, defined as classical-like EDS (clEDS), since it phenotypically resembles the classical form of EDS, though lacking atrophic scarring.
Although the precise role of TNX in the pathogenesis of EDS is uncertain, this patient's findings suggest a unique and essential role for TNX in connective-tissue structure and function.
An overlapping phenotype of Osteogenesis imperfecta and Ehlers-Danlos syndrome due to a heterozygous mutation in COL1A1 and biallelic missense variants in TNXB identified by whole exome sequencing.
Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme, we suggested that tenascin-X might regulate collagen synthesis or deposition.
Because of the limited awareness among geneticists and the challenge of the molecular analysis of the TNXB gene, the TNX-deficient type EDS is probably to be under diagnosed.
Because of the reported cardiovascular abnormalities in other EDS types and the excessive haematoma formation after mild trauma in TNX-deficient individuals, we investigated whether cardiovascular or coagulation abnormalities occur in these patients.
Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS.
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.
Further evaluation of these mice showed that tenascin-X is an important regulator of collagen deposition in vivo, suggesting a novel mechanism of disease in this form of EDS.
Given that TNXB is a functional candidate gene for EDS, we suggest that compound heterozygosity for the identified TNXB variants may have caused the EDS-like phenotype in the affected dog.
Heterozygosity for TNXB mutations causing haploinsufficiency of TNX may be associated with the mild "hypermobility form" of EDS, which principally affects small and large joints.
High-Throughput Screening for CYP21A1P-TNXA/TNXB Chimeric Genes Responsible for Ehlers-Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia.
Light microscopic and ultrastructural changes of the elastic fibers were observed in TNX-haploinsufficient hypermobility type EDS patients, which were not found in hypermobility type EDS patients in whom TNX mutations were excluded.
Moreover, the study of these diseases has brought new insights into the molecular pathogenesis of EDS by implicating genetic defects in the biosynthesis of other extracellular matrix (ECM) molecules, such as proteoglycans and tenascin-X, or genetic defects in molecules involved in intracellular trafficking, secretion and assembly of ECM proteins.
Patients with tenascin-X (TNX)-deficient type Ehlers-Danlos syndrome (EDS) do not exhibit delayed wound healing, unlike classic type EDS patients, who exhibit mutations in collagen genes.