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A homozygous recurring mutation in WISP3 causing progressive pseudorheumatoid arthropathy
Fatih Temiz1, Mehmet Nuri Ozbek, Damla Kotan
1Department of Pediatric Endocrinology and Metabolism, Cukurova University Faculty of Medicine, Balcali, Adana, Turkey. ftemiz2003@yahoo.com
Summary
Mutations in the WISP3 gene cause progressive pseudorheumatoid arthropathy of childhood (PPAC), a rare skeletal disorder. Identifying the specific WISP3 mutation offers a rapid diagnosis for affected children.
Area of Science:
- Genetics
- Molecular Biology
- Skeletal Dysplasias
Background:
- WISP3 (CCN family) encodes secreted proteins regulating cell growth and differentiation.
- Mutations in WISP3 are linked to autosomal recessive skeletal disorders like progressive pseudorheumatoid arthropathy of childhood (PPAC).
Observation:
- Three siblings from a non-consanguineous family presented with PPAC.
- Disease onset between ages 2-8 years included joint stiffness, swelling, osteopenia, and growth delay.
- Genetic analysis revealed a homozygous Cys52-to-ter (C52X) mutation in the WISP3 gene.
Findings:
- The identified C52X WISP3 mutation was previously reported in diverse ethnic groups.
- A linked c.248G-->A (G83E) variation suggests a possible founder effect or mutational hotspot.
- Normal levels of growth hormone, IGF-1, IGFBP-3, glucose, and insulin were observed.
Implications:
- Recognizing this rare WISP3-related disorder aids in avoiding misdiagnoses and unnecessary treatments.
- Genetic testing for the specific WISP3 mutation provides a swift and accurate diagnosis for suspected PPAC cases.
- Understanding WISP3's role is crucial for comprehending skeletal development and associated pathologies.
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