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Licensed Unlicensed Requires Authentication Published by De Gruyter March 16, 2011

A homozygous recurring mutation in WISP3 causing progressive pseudorheumatoid arthropathy

Fatih Temiz EMAIL logo , Mehmet Nuri Ozbek , Damla Kotan , Ozlem Sangun , Neslihan Onenli Mungan , Bilgin Yuksel and Ali Kemal Topaloglu
From the journal

Abstract

WISP3 is a member of the CCN (for CTGF, CYR61, and NOV) gene family, which encodes cysteine-rich secreted proteins with roles in cell growth and differentiation. Mutations in the WISP3 gene are associated with the autosomal recessive skeletal disorder, also known as progressive pseudorheumatoid arthropathy of childhood (PPAC). We diagnosed three siblings from a non-consanguineous family with PPAC. The patients were asymptomatic in early childhood. Signs and symptoms of disease that include progressive joint stiffness, swelling of the finger joints, and osteopenia, and slow linear growth developed between 2 and 8 years of age. PCR amplification and direct sequencing of the WISP3 gene revealed a homozygous mutation at nucleotide 156 of the WISP3 gene, resulting in a Cys52-to-ter substitution. This mutation has previously been reported in French, Italian, and Arab families. Interestingly, the C52X mutation was found to be associated with a c.248G→A (G83E) variation, suggesting the existence of a founder effect. By contrast, the presence of the same aberration in three different ethnic groups could imply that this particular site is prone to mutation. Basal fasting concentrations of growth hormone, insulin-like growth factor-1, and insulin-like growth factor binding protein-3, as well as glucose and insulin levels revealed no aberrations. In conclusion, consideration of this rare disease that causes significant morbidity with short stature, osteopenia and arthritic complaints would prevent unnecessary examinations and treatment attempts. Testing for this specific mutation in suspected cases could provide a rapid and definitive diagnosis.


Corresponding author: Fatih Temiz, MD, Department of Pediatric Endocrinology and Metabolism, Cukurova University Faculty of Medicine, Balcali, 01330 Adana, Turkey Phone/Fax: + 90 322 338 70 83

Published Online: 2011-03-16
Published in Print: 2011-03-01

©2011 by Walter de Gruyter Berlin New York

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