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. 2018 Feb 1;4(1):a001990.
doi: 10.1101/mcs.a001990. Print 2018 Feb.

WISP3 mutation associated with pseudorheumatoid dysplasia

M Reza Sailani  1 , James Chappell  1 , Inlora Jingga  1 , Anil Narasimha  1 , Amin Zia  1 , Janet Linnea Lynch  1 , Safoura Mazrouei  2 , Jonathan A Bernstein  3 , Omid Aryani  4   5 , Michael P Snyder  1
Affiliations

WISP3 mutation associated with pseudorheumatoid dysplasia

M Reza Sailani et al. Cold Spring Harb Mol Case Stud. .

Abstract

Progressive pseudorheumatoid dysplasia (PPD) is a skeletal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness. Here we report genetic characterization of a consanguineous family segregating an uncharacterized from of skeletal dysplasia. Whole-exome sequencing of four affected siblings and their parents identified a loss-of-function homozygous mutation in the WISP3 gene, leading to diagnosis of PPD in the affected individuals. The identified variant (Chr6: 112382301; WISP3:c.156C>A p.Cys52*) is rare and predicted to cause premature termination of the WISP3 protein.

Keywords: multiple skeletal anomalies; spondyloepimetaphyseal dysplasia.

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Figures

Figure 1.
Figure 1.
(A) Pedigree structure of the PPD family. The star shows family members from whom DNA samples were available and sequenced. (B) Sanger sequencing traces (TGC/AAA) showing the c.156C>A; p.Cys52* mutation in the WISP3 gene. The segregation of this mutation has been confirmed in six available DNA samples from this family.
Figure 2.
Figure 2.
Schematic of the WISP3 protein. Amino acid residue numbers are indicated above each domain. The number of unique mutations and the number of affected families described are indicated below the domains. WISP3 contains a signaling peptide (SP) and four conserved cysteine-rich domains: insulin-like growth factor–binding domain (IGFBP), von Willebrand factor type C module (VWC), thrombospondin domain (TSP), and carboxy-terminal cystine knot–like domain (CTCK). The * indicates where c.156C>A occurs.
See this image and copyright information in PMC

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