Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia

Jennifer R. Hurvitz, Wafaa M. Suwairi, Wim Van Hul, Hatem El-Shanti, Andrea Superti-Furga, Jean Roudier, Daniel Holderbaum, Richard M. Pauli, J. Kenneth Herd, Els Van Hul, Hossien Rezai-Delui, Eric Legius, Martine Le Merrer, Jamil Al-Alami, Sultan A. Bahabri, Matthew L. Warman

Research output: Contribution to journalArticle

189 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)94-98
Number of pages5
JournalNature Genetics
Volume23
Issue number1
DOIs
Publication statusPublished - 1999
Externally publishedYes

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Tuberculin
Cartilage
Mutation
Replacement Arthroplasties
Growth
Genes
Middle East
Juvenile Arthritis
Essential Genes
Chondrocytes
Diagnostic Errors
Signs and Symptoms
Cysteine
Cell Differentiation
Homeostasis
Organizations
Biopsy
Bone and Bones
Incidence
Population

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Hurvitz, J. R., Suwairi, W. M., Van Hul, W., El-Shanti, H., Superti-Furga, A., Roudier, J., ... Warman, M. L. (1999). Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Nature Genetics, 23(1), 94-98. https://doi.org/10.1038/12699

Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. / Hurvitz, Jennifer R.; Suwairi, Wafaa M.; Van Hul, Wim; El-Shanti, Hatem; Superti-Furga, Andrea; Roudier, Jean; Holderbaum, Daniel; Pauli, Richard M.; Herd, J. Kenneth; Van Hul, Els; Rezai-Delui, Hossien; Legius, Eric; Le Merrer, Martine; Al-Alami, Jamil; Bahabri, Sultan A.; Warman, Matthew L.

In: Nature Genetics, Vol. 23, No. 1, 1999, p. 94-98.

Research output: Contribution to journalArticle

Hurvitz, JR, Suwairi, WM, Van Hul, W, El-Shanti, H, Superti-Furga, A, Roudier, J, Holderbaum, D, Pauli, RM, Herd, JK, Van Hul, E, Rezai-Delui, H, Legius, E, Le Merrer, M, Al-Alami, J, Bahabri, SA & Warman, ML 1999, 'Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia', Nature Genetics, vol. 23, no. 1, pp. 94-98. https://doi.org/10.1038/12699
Hurvitz JR, Suwairi WM, Van Hul W, El-Shanti H, Superti-Furga A, Roudier J et al. Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. Nature Genetics. 1999;23(1):94-98. https://doi.org/10.1038/12699
Hurvitz, Jennifer R. ; Suwairi, Wafaa M. ; Van Hul, Wim ; El-Shanti, Hatem ; Superti-Furga, Andrea ; Roudier, Jean ; Holderbaum, Daniel ; Pauli, Richard M. ; Herd, J. Kenneth ; Van Hul, Els ; Rezai-Delui, Hossien ; Legius, Eric ; Le Merrer, Martine ; Al-Alami, Jamil ; Bahabri, Sultan A. ; Warman, Matthew L. / Mutations in the CCN gene family member WISP3 cause progressive pseudorheumatoid dysplasia. In: Nature Genetics. 1999 ; Vol. 23, No. 1. pp. 94-98.
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