PubMed:11642233 JSONTXT

{"project":"PubMed_Structured_Abstracts","denotations":[{"id":"T1","span":{"begin":92,"end":546},"obj":"BACKGROUND"},{"id":"T2","span":{"begin":556,"end":989},"obj":"METHODS"},{"id":"T3","span":{"begin":999,"end":1920},"obj":"RESULTS"},{"id":"T4","span":{"begin":1934,"end":2241},"obj":"CONCLUSIONS"}],"text":"A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.\nBACKGROUND: The Ehlers-Danlos syndrome is a heritable connective-tissue disorder caused by defects in fibrillar-collagen metabolism. Mutations in the type V collagen genes account for up to 50 percent of cases of classic Ehlers-Danlos syndrome, but many other cases are unexplained. We investigated whether the deficiency of the tenascins, extracellular-matrix proteins that are highly expressed in connective tissues, was associated with the Ehlers-Danlos syndrome.\nMETHODS: We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers-Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. We examined the expression of tenascins and type V collagen in skin by immunohistochemical methods and sequenced the tenascin-X gene.\nRESULTS: Tenascin-X was present in serum from all normal subjects, all patients with psoriasis, all patients with rheumatoid arthritis, and 146 of 151 patients with the Ehlers-Danlos syndrome. Tenascin-X was absent from the serum of the 5 remaining patients with Ehlers-Danlos syndrome, who were unrelated. Tenascin-X deficiency was confirmed in these patients by analysis of skin fibroblasts and by immunostaining of skin. The expression of tenascin-C and type V collagen was normal in these patients. All five of these patients had hypermobile joints, hyperelastic skin, and easy bruising, without atrophic scarring. Tenascin-X mutations were identified in all tenascin-X-deficient patients; one patient had a homozygous tenascin-X gene deletion, one was heterozygous for the deletion, and three others had homozygous truncating point mutations, confirming a causative role for tenascin-X and a recessive pattern of inheritance.\nCONCLUSIONS: Tenascin-X deficiency causes a clinically distinct, recessive form of the Ehlers-Danlos syndrome. This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"11642233-12#0#10#gene7148","span":{"begin":1934,"end":1944},"obj":"gene7148"},{"id":"11642233-12#74#96#diseaseC0013720","span":{"begin":2008,"end":2030},"obj":"diseaseC0013720"},{"id":"11642233-13#147#157#gene7148","span":{"begin":2179,"end":2189},"obj":"gene7148"},{"id":"11642233-13#102#114#diseaseC1857276","span":{"begin":2134,"end":2146},"obj":"diseaseC1857276"},{"id":"11642233-4#236#246#gene7148","span":{"begin":792,"end":802},"obj":"gene7148"},{"id":"11642233-4#171#191#diseaseC0003873","span":{"begin":727,"end":747},"obj":"diseaseC0003873"},{"id":"11642233-6#0#10#gene7148","span":{"begin":999,"end":1009},"obj":"gene7148"},{"id":"11642233-6#76#85#diseaseC0033860","span":{"begin":1075,"end":1084},"obj":"diseaseC0033860"}],"relations":[{"id":"0#10#gene714874#96#diseaseC0013720","pred":"associated_with","subj":"11642233-12#0#10#gene7148","obj":"11642233-12#74#96#diseaseC0013720"},{"id":"147#157#gene7148102#114#diseaseC1857276","pred":"associated_with","subj":"11642233-13#147#157#gene7148","obj":"11642233-13#102#114#diseaseC1857276"},{"id":"236#246#gene7148171#191#diseaseC0003873","pred":"associated_with","subj":"11642233-4#236#246#gene7148","obj":"11642233-4#171#191#diseaseC0003873"},{"id":"0#10#gene714876#85#diseaseC0033860","pred":"associated_with","subj":"11642233-6#0#10#gene7148","obj":"11642233-6#76#85#diseaseC0033860"}],"text":"A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.\nBACKGROUND: The Ehlers-Danlos syndrome is a heritable connective-tissue disorder caused by defects in fibrillar-collagen metabolism. Mutations in the type V collagen genes account for up to 50 percent of cases of classic Ehlers-Danlos syndrome, but many other cases are unexplained. We investigated whether the deficiency of the tenascins, extracellular-matrix proteins that are highly expressed in connective tissues, was associated with the Ehlers-Danlos syndrome.\nMETHODS: We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers-Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. We examined the expression of tenascins and type V collagen in skin by immunohistochemical methods and sequenced the tenascin-X gene.\nRESULTS: Tenascin-X was present in serum from all normal subjects, all patients with psoriasis, all patients with rheumatoid arthritis, and 146 of 151 patients with the Ehlers-Danlos syndrome. Tenascin-X was absent from the serum of the 5 remaining patients with Ehlers-Danlos syndrome, who were unrelated. Tenascin-X deficiency was confirmed in these patients by analysis of skin fibroblasts and by immunostaining of skin. The expression of tenascin-C and type V collagen was normal in these patients. All five of these patients had hypermobile joints, hyperelastic skin, and easy bruising, without atrophic scarring. Tenascin-X mutations were identified in all tenascin-X-deficient patients; one patient had a homozygous tenascin-X gene deletion, one was heterozygous for the deletion, and three others had homozygous truncating point mutations, confirming a causative role for tenascin-X and a recessive pattern of inheritance.\nCONCLUSIONS: Tenascin-X deficiency causes a clinically distinct, recessive form of the Ehlers-Danlos syndrome. This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix."}

{"project":"DisGeNET","denotations":[{"id":"T0","span":{"begin":999,"end":1009},"obj":"gene:7148"},{"id":"T1","span":{"begin":1159,"end":1181},"obj":"disease:C0013720"}],"relations":[{"id":"R1","pred":"associated_with","subj":"T0","obj":"T1"}],"namespaces":[{"prefix":"gene","uri":"http://www.ncbi.nlm.nih.gov/gene/"},{"prefix":"disease","uri":"http://purl.bioontology.org/ontology/MEDLINEPLUS/"}],"text":"A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency.\nBACKGROUND: The Ehlers-Danlos syndrome is a heritable connective-tissue disorder caused by defects in fibrillar-collagen metabolism. Mutations in the type V collagen genes account for up to 50 percent of cases of classic Ehlers-Danlos syndrome, but many other cases are unexplained. We investigated whether the deficiency of the tenascins, extracellular-matrix proteins that are highly expressed in connective tissues, was associated with the Ehlers-Danlos syndrome.\nMETHODS: We screened serum samples from 151 patients with the classic, hypermobility, or vascular types of the Ehlers-Danlos syndrome; 75 patients with psoriasis; 93 patients with rheumatoid arthritis; and 21 healthy persons for the presence of tenascin-X and tenascin-C by enzyme-linked immunosorbent assay. We examined the expression of tenascins and type V collagen in skin by immunohistochemical methods and sequenced the tenascin-X gene.\nRESULTS: Tenascin-X was present in serum from all normal subjects, all patients with psoriasis, all patients with rheumatoid arthritis, and 146 of 151 patients with the Ehlers-Danlos syndrome. Tenascin-X was absent from the serum of the 5 remaining patients with Ehlers-Danlos syndrome, who were unrelated. Tenascin-X deficiency was confirmed in these patients by analysis of skin fibroblasts and by immunostaining of skin. The expression of tenascin-C and type V collagen was normal in these patients. All five of these patients had hypermobile joints, hyperelastic skin, and easy bruising, without atrophic scarring. Tenascin-X mutations were identified in all tenascin-X-deficient patients; one patient had a homozygous tenascin-X gene deletion, one was heterozygous for the deletion, and three others had homozygous truncating point mutations, confirming a causative role for tenascin-X and a recessive pattern of inheritance.\nCONCLUSIONS: Tenascin-X deficiency causes a clinically distinct, recessive form of the Ehlers-Danlos syndrome. This finding indicates that factors other than the collagens or collagen-processing enzymes can cause the syndrome and suggests a central role for tenascin-X in maintaining the integrity of collagenous matrix."}