title: WISP3 mutational analysis in Indian patients diagnosed with progressive pseudorheumatoid dysplasia and report of a novel mutation at p.Y198.
abstract: OBJECTIVE
  To determine the pattern of mutations of the WISP3 gene in clinically identified progressive pseudorheumatoid dysplasia (PPD) in an Indian population.
  
  
  METHODS
  A total of 15 patients with clinical features of PPD were enrolled in this study. Genomic DNA was isolated and polymerase chain reaction performed to amplify the WISP3 gene. Screening for mutations was done by conformation-sensitive gel electrophoresis, beginning with the fifth exon and subsequently proceeding to the remaining exons. Sanger sequencing was performed for both forward and reverse strands to confirm the mutations.
  
  
  RESULTS
  In all, two of the 15 patients had compound heterozygous mutations: one a nonsense mutation c.156C>A (p.C52*) in exon 2, and the other a missense mutation c.677G>T (p.G226V) in exon 4. All others were homozygous, with three bearing a nonsense mutation c.156C>A (p.C52*) in exon 2, three a missense mutation c.233G>A (p.C78Y) in exon 2, five a missense mutation c.1010G>A (p.C337Y) in exon 5, one a nonsense mutation c.348C>A (p.Y116*) in exon 3, and one with a novel deletion mutation c.593_597delATAGA (p.Y198*) in exon 4.
  
  
  CONCLUSIONS
  We identified a novel mutation c.593_597delATAGA (p.Y198*) in the fourth exon of the WISP3 gene. We also confirmed c.1010G>A as one of the common mutations in an Indian population with progressive pseudorheumatoid dysplasia.Cite this article: V. Madhuri, M. Santhanam, K. Rajagopal, L. K. Sugumar, V. Balaji. WISP3 mutational analysis in Indian patients diagnosed with progressive pseudorheumatoid dysplasia and report of a novel mutation at p.Y198* Bone Joint Res 2016;5:301-306. DOI: 10.1302/2046-3758.57.2000520.
authors.affiliation: Paediatric Orthopaedics Unit, Department of Orthopaedics, Christian Medical College, Vellore, Tamil Nadu, 632004, India and Adjunct Scientist, Centre for Stem Cell Research (a unit of inStem, Bengaluru), Christian Medical College, Vellore, Tamil Nadu, 632002, India madhuriwalter@cmcvellore.ac.in.
authors.forename: V
authors.initials: V
authors.lastname: Madhuri
authors.affiliation: Paediatric Orthopaedics Unit, Department of Orthopaedics, Christian Medical College, Vellore, Tamil Nadu, 632004, India.
authors.forename: M
authors.initials: M
authors.lastname: Santhanam
authors.affiliation: Paediatric Orthopaedics Unit, Department of Orthopaedics, Christian Medical College, Vellore, Tamil Nadu, 632004, India.
authors.forename: K
authors.initials: K
authors.lastname: Rajagopal
authors.affiliation: Paediatric Orthopaedics Unit, Department of Orthopaedics, Christian Medical College, Vellore, Tamil Nadu, 632004, India.
authors.forename: L K
authors.initials: LK
authors.lastname: Sugumar
authors.affiliation: Paediatric Orthopaedics Unit, Department of Orthopaedics, Christian Medical College, Vellore, Tamil Nadu, 632004, India.
authors.forename: V
authors.initials: V
authors.lastname: Balaji
keywords: Platyspondyly; Progressive pseudorheumatoid dysplasia; Spondyloepiphyseal dysplasia; WISP3; c.1010G>A (p.C337Y)