A Novel Deletion Mutation in Proteoglycan-4 Underlies Camptodactyly-Arthropathy-Coxa-Vara-Pericarditis Syndrome in a Consanguineous Pakistani Family

Basit, Sulman; Iqbal, Zafar; Umicevic-Mirkov, Masha; Naqvi, Syed Kamran ul-Hassan; Coenen, Marieke J.H.; Ansar, Muhammad; Bokhoven, Hans van; Ahmad, Wasim

doi:10.1016/j.arcmed.2011.04.006

Cited by 17 publications

(19 citation statements)

References 14 publications

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“…The ADAMTSs are extracellular multidomain enzymes with multiple functions: (i) collagen processing as procollagen N-proteinase, (ii) cleavage of the matrix proteoglycans aggrecan, versican, and brevican, (iii) inhibition of angiogenesis, and (iv) blood coagulation homoeostasis as the von Willebrand factor cleaving protease [154]. Adamts5 is comprised from N- to C-terminus: (i) a signal peptide, (ii) a prodomain, (iii) a metalloproteinase domain, (iv) a disintegrin domain, (v) a thrombospondin type motif (TSP Type-I), (vi) a cysteine-rich domain, (vii) a spacer region, and (viii) TSP type-I motif [149]. ADAMTS5 is a C- and O-glycosylated molecule.…”

Section: Glycoproteins Adamts5 and Other Proteoglycansmentioning

confidence: 99%

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Defects in Tendon, Ligament, and Enthesis in Response to Genetic Alterations in Key Proteoglycans and Glycoproteins: A Review

Juneja

Veillette

2013

Arthritis

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This review summarizes the genetic alterations and knockdown approaches published in the literature to assess the role of key proteoglycans and glycoproteins in the structural development, function, and repair of tendon, ligament, and enthesis. The information was collected from (i) genetically altered mice, (ii) in vitro knockdown studies, (iii) genetic variants predisposition to injury, and (iv) human genetic diseases. The genes reviewed are for small leucine-rich proteoglycans (lumican, fibromodulin, biglycan, decorin, and asporin); dermatan sulfate epimerase (Dse) that alters structure of glycosaminoglycan and hence the function of small leucine-rich proteoglycans by converting glucuronic to iduronic acid; matricellular proteins (thrombospondin 2, secreted phosphoprotein 1 (Spp1), secreted protein acidic and rich in cysteine (Sparc), periostin, and tenascin X) including human tenascin C variants; and others, such as tenomodulin, leukocyte cell derived chemotaxin 1 (chondromodulin-I, ChM-I), CD44 antigen (Cd44), lubricin (Prg4), and aggrecan degrading gene, a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 5 (Adamts5). Understanding these genes represents drug targets for disrupting pathological mechanisms that lead to tendinopathy, ligamentopathy, enthesopathy, enthesitis and tendon/ligament injury, that is, osteoarthritis and ankylosing spondylitis.

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Section: Glycoproteins Adamts5 and Other Proteoglycansmentioning

confidence: 99%

“…A deletion mutation was found in Prg4 gene in a family with CACP. Sequence analysis of Prg4 gene in the affected individuals revealed a 2-base-pair deletion predicting a frame shift mutation [149, Table I].…”

Section: Glycoproteins Adamts5 and Other Proteoglycansmentioning

confidence: 99%

Defects in Tendon, Ligament, and Enthesis in Response to Genetic Alterations in Key Proteoglycans and Glycoproteins: A Review

Juneja

Veillette

2013

Arthritis

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“…11 To date, 15 mutations in the PRG4 gene have been reported, which are associated with CACP syndrome in 20 affected patients mainly of Arabian origin. 4,[12][13][14] In the present study, we report the results of PRG4 gene molecular analysis in 13 European patients, from 10 unrelated families, who were diagnosed with CACP syndrome. We identified novel mutations in the cohort analyzed.…”

Section: Introductionmentioning

confidence: 99%

CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort

et al. 2013

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“…Furthermore, mutations in the gene encoding the secretion of PRG4 lead to synovial hyperplasia and loss of its lubricating function, which is the principal pathological feature of this syndrome (7,8). Currently, there are 15 reported PRG4 mutations (9,10,11). …”

Section: Introductionmentioning

confidence: 99%

“…Although, it has been described in different ethnicities, the diagnosis of CACP syndrome in Saudi families is relatively frequent (9,12,13,14). Unfortunately, there is no available effective treatment yet.…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of Yttrium-90 Radiosynovectomy in Patients with Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome

Al‐Mayouf

Almutairi²,

Al‐Ismail³

2017

Mirt

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Objective:Camptodactyly-arthropathy-coxa-vara-pericarditis (CACP) syndrome is an autosomal recessive disorder caused by mutations in PRG4 gene that encodes for proteoglycan 4, the main lubricant for joints and tendon surfaces. It is a non-inflammatory arthropathy, characterized by joint effusions and synovial hypertrophy. So far, there is no effective treatment for this disorder. To evaluate the effectiveness of yttrium-90 radiosynovectomy in arthropathy of patients with CACP syndrome.Methods:Consecutive patients with CACP syndrome were prospectively evaluated at the enrollment and 3 months after the right knee injection with yttrium-90. The outcome variables were patient/parent and physician’s global assessment measured by a 3-point scale, right knee swelling and range of motion on a 3-point scale, in addition to magnetic resonance imaging (MRI) assessment of the right knee for bone, cartilage, fluid, synovial hypertrophy and soft tissue changes.Results:Six (three boys, three girls) patients with a mean age of 12 years and mean follow-up duration of 8.5 years completed a single right knee intra-articular yttrium-90 injection with 5 mCi. The procedure was well tolerated without adverse events apart from mild and transient joint pain in two patients. There was a minimal radioisotope leakage to soft tissue in two patients. During the 3-month follow-up interval, there was no improvement in the outcome variables. Patients and parents did not notice favorable therapeutic effects and global physician assessment was unsatisfactory. There was no difference in knee joint swelling or range of motion. Furthermore, MRI findings were unchanged. However, there was a minimal increase in synovial fluid post injection.Conclusion:Yttrium-90 radiosynovectomy seems to be a safe and well tolerated procedure, however, it did not show a beneficial therapeutic effect in arthropathy of CACP syndrome with the given dosage and interval. Studies including a larger number of patients and probably repeated injections are needed to derive satisfactory results about the effectiveness of yttrium-90 in CACP syndrome patients.

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A Novel Deletion Mutation in Proteoglycan-4 Underlies Camptodactyly-Arthropathy-Coxa-Vara-Pericarditis Syndrome in a Consanguineous Pakistani Family

Cited by 17 publications

References 14 publications

Defects in Tendon, Ligament, and Enthesis in Response to Genetic Alterations in Key Proteoglycans and Glycoproteins: A Review

Defects in Tendon, Ligament, and Enthesis in Response to Genetic Alterations in Key Proteoglycans and Glycoproteins: A Review

CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort

The Efficacy of Yttrium-90 Radiosynovectomy in Patients with Camptodactyly-Arthropathy-Coxa Vara-Pericarditis Syndrome

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