Haiyang Luo1, Changhe Shi1, Chengyuan Mao2, Chenyang Jiang2, Deming Bao3, Jinyan Guo4, Pan Du5, Yaohe Wang5, Yutao Liu1, Xinjing Liu1, Bo Song1, Yuming Xu6. 1. Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China. 2. 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. 3. Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China. 4. Department of Rheumatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 Jian-she East Road, Zhengzhou 450000, Henan, China. 5. 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. 6. 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.
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. MATERIALS AND 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.
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. MATERIALS AND 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: Sofia Torreggiani; Marta Torcoletti; Belinda Campos-Xavier; Francesco Baldo; Carlo Agostoni; Andrea Superti-Furga; Giovanni Filocamo Journal: Rheumatol Int Date: 2018-10-16 Impact factor: 2.631
Authors: M Reza Sailani; James Chappell; Inlora Jingga; Anil Narasimha; Amin Zia; Janet Linnea Lynch; Safoura Mazrouei; Jonathan A Bernstein; Omid Aryani; Michael P Snyder Journal: Cold Spring Harb Mol Case Stud Date: 2018-02-01
Authors: Ali Al Kaissi; Vladimir Kenis; Lamia Ben Jemaa; Hela Sassi; Mohammad Shboul; Franz Grill; Rudolf Ganger; Susanne Gerit Kircher Journal: Clin Rheumatol Date: 2019-10-18 Impact factor: 2.980