title: A novel compound WISP3 mutation in a Chinese family with progressive pseudorheumatoid dysplasia.
abstract: BACKGROUND
  Progressive pseudorheumatoid dysplasia (PPD) is an extremely rare autosomal recessive genetic disease caused by mutation of the Wnt1-inducible signaling pathway protein 3 (WISP3) gene. Here, we characterize the clinical manifestations and features of PPD and screen for WISP3 mutations.
  
  
  METHODS
  We performed genetic testing for PPD in a Chinese family, after investigating the clinical particulars and family history, in addition to 200 healthy individuals, who served as the controls for this study. All 5 exons and the exon-intron boundaries of the WISP3 gene were amplified by polymerase chain reaction (PCR) and sequenced directly.
  
  
  RESULTS
  We identified a missense mutation (c.667T>G, p.C223G) in the maternal allele and a nonsense mutation (c.756C>A, p.C252X) in the paternal allele in the two affected individuals. To our knowledge, the mutation c.756C>A has not been reported previously. In these patients, there was a specific period when their condition markedly improved after having been very serious. Moreover, severe compression of lumbar spinal cord led to conspicuous spinal disorders in the proband.
  
  
  CONCLUSIONS
  Our study suggests that novel C223G and C252X mutations in exon 4 of the WISP3 gene are responsible for PPD in Chinese patients. Furthermore, we report certain unique phenotypic characteristics in our patients.
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Haiyang
authors: H
authors: Luo
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Changhe
authors: C
authors: Shi
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, China.
authors: Chengyuan
authors: C
authors: Mao
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China; Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, China.
authors: Chenyang
authors: C
authors: Jiang
authors: Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Deming
authors: D
authors: Bao
authors: Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Jinyan
authors: J
authors: Guo
authors: International Joint Research Laboratory for Cell and Gene Therapy of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Pan
authors: P
authors: Du
authors: International Joint Research Laboratory for Cell and Gene Therapy of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Yaohe
authors: Y
authors: Wang
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Yutao
authors: Y
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Xinjing
authors: X
authors: Liu
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China.
authors: Bo
authors: B
authors: Song
authors: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China. Electronic address: xuyuming@zzu.edu.cn.
authors: Yuming
authors: Y
authors: Xu
mesh_terms: D001177:Arthropathy, Neurogenic / Q000000981:diagnostic imaging / Q000235:genetics*; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics*; D002681:China; D018389:Codon, Nonsense; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D007592:Joint Diseases / Q000151:congenital; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011859:Radiography; D055815:Young Adult
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human; D018389:Codon, Nonsense
keywords: Mutation; Progressive pseudorheumatoid dysplasia; Spinal disorder; WISP3