A novel compound WISP3 mutation in a Chinese family with progressive pseudorheumatoid dysplasia

• Our study identified a novel compound heterozygous mutation in WISP3 gene of PPD patients.
• This is the first report that there seems to be a long remission of PPD patients.
• Our study will be helpful for the diagnosis and treatment for the PPD patients

BackgroundProgressive 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 methodsWe 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.ResultsWe 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.ConclusionsOur 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.