Journal article
Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia
Nature genetics, Vol.23(1), pp.94-98
09/1999
DOI: 10.1038/12699
PMID: 10471507
Abstract
Members of the CCN (for CTGF, cyr61/cef10, nov) gene family encode cysteine-rich secreted proteins with roles in cell growth and differentiation. Cell-specific and tissue-specific differences in the expression and function of different CCN family members suggest they have non-redundant roles. Using a positional-candidate approach, we found that mutations in the CCN family member WISP3 are associated with the autosomal recessive skeletal disorder progressive pseudorheumatoid dysplasia (PPD; MIM 208230). PPD is an autosomal recessive disorder that may be initially misdiagnosed as juvenile rheumatoid arthritis. Its population incidence has been estimated at 1 per million in the United Kingdom, but it is likely to be higher in the Middle East and Gulf States. Affected individuals are asymptomatic in early childhood. Signs and symptoms of disease typically develop between three and eight years of age. Clinically and radiographically, patients experience continued cartilage loss and destructive bone changes as they age, in several instances necessitating joint replacement surgery by the third decade of life. Extraskeletal manifestations have not been reported in PPD. Cartilage appears to be the primary affected tissue, and in one patient, a biopsy of the iliac crest revealed abnormal nests of chondrocytes and loss of normal cell columnar organization in growth zones. We have identified nine different WISP3 mutations in unrelated, affected individuals, indicating that the gene is essential for normal post-natal skeletal growth and cartilage homeostasis.
Details
- Title: Subtitle
- Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia
- Creators
- Els Van Hul - Department of Medical Genetics, University of AntwerpMatthew L Warman - Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of ClevelandJamil Al-Alami - Departments of Biochemistry and Medical Laboratory Sciences, Jordan University of Science and TechnologyJean Roudier - Immunorheumatology, INSERM E9940, Universitéde la MéditerranéeSultan A Bahabri - King Faisal Specialist Hospital and Research CenterJennifer R Hurvitz - Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of ClevelandRichard M Pauli - Division of Genetics, Children's Hospital, University of WisconsinHatem El-Shanti - Departments of Pediatrics and Medical Laboratory Sciences, Jordan University of Science and TechnologyHossien Rezai-Delui - Department of Radiology, Mashad University, Ghaen HospitalWim Van Hul - Department of Medical Genetics, University of AntwerpWafaa M Suwairi - Department of Genetics and Center for Human Genetics, Case Western Reserve University School of Medicine and University Hospitals of Cleveland Department of Pediatrics, Royal Military Hospital King Faisal Specialist Hospital and Research CenterEric Legius - Centre for Human Genetics, Catholic University of LeuvenDaniel Holderbaum - Division of Rheumatology, Department of Medicine, University Hospitals of ClevelandJ. Kenneth Herd - Department of Pediatrics, East Tennessee State University, James H. Quillen College of MedicineAndrea Superti-Furga - Division of Molecular Pediatrics, Department of Pediatrics, University of ZurichMartine Le Merrer - Department of Genetics and INSERM U393, Hospital Necker Enfants Malades
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.23(1), pp.94-98
- DOI
- 10.1038/12699
- PMID
- 10471507
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English
- Date published
- 09/1999
- Academic Unit
- Stead Family Department of Pediatrics; Medical Genetics and Genomics
- Record Identifier
- 9984093341602771
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