title: A homozygous recurring mutation in WISP3 causing progressive pseudorheumatoid arthropathy.
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.
authors.affiliation: Department of Pediatric Endocrinology and Metabolism, Cukurova University Faculty of Medicine, Balcali, Adana, Turkey. ftemiz2003@yahoo.com
authors.forename: Fatih
authors.initials: F
authors.lastname: Temiz
authors.forename: Mehmet Nuri
authors.initials: MN
authors.lastname: Ozbek
authors.forename: Damla
authors.initials: D
authors.lastname: Kotan
authors.forename: Ozlem
authors.initials: O
authors.lastname: Sangun
authors.forename: Neslihan Onenli
authors.initials: NO
authors.lastname: Mungan
authors.forename: Bilgin
authors.initials: B
authors.lastname: Yuksel
authors.forename: Ali Kemal
authors.initials: AK
authors.lastname: Topaloglu
mesh_terms: D000293:Adolescent; D001177:Arthropathy, Neurogenic / Q000235:genetics; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D007592:Joint Diseases / Q000151:congenital; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human; D018969:Insulin-Like Growth Factor Binding Proteins