WISP3 mutational analysis in Indian patients diagnosed with progressive pseudorheumatoid dysplasia and report of a novel mutation at p.Y198*

Abstract

ObjectivesTo determine the pattern of mutations of the WISP3 gene in clinically identified progressive pseudorheumatoid dysplasia (PPD) in an Indian population.Patients and MethodsA 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.ResultsIn 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.ConclusionWe 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.

CCN6 mutation detection in Chinese patients with progressive pseudo‐rheumatoid dysplasia and identification of four novel mutations

“…In the present study, radiological features consisted of irregular narrow interphalangeal (four patients, Figure 5a), wrist (one patients, Figure 5a), hip (four patients, Figure 5b), knee (three patients, Figure 5c-d), and ankle (one patients, Figure 5e) joint spaces, along with scoliosis and platyspondylia (three patients) (Figure 5g,h). Enlarged metaphysis of the femoral head, short and wide femoral necks, and enlarged tibial metaphysis can be seen in Figure 5b,c Madhuri et al, 2016;Spranger, Albert, Schilling, Bartsocas, & Opitz, 1983;Teebi & Al Awadi, 1986;Temiz et al, 2011;Wynne-Davies et al, 1982). Additionally, the inflammatory parameters of five patients are as follows: normal c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels; negative rheumatoid factor (RF) and autoantibodies such as anti-nuclear antibodies, anti-cyclic citrullinated peptide (CCP) antibody, and anti-citrullinated protein antibodies.…”

“…Skeletal changes become increasingly apparent with time and are responsible for the flexion deformities, such as hips and knees. Scoliosis and short trunk can also be observed (Delague et al, 2005;Gao et al, 2013;Luo et al, 2015;Madhuri, Santhanam, Rajagopal, Sugumar, & Balaji, 2016;Sun et al, 2012;Yan et al, 2016;Ye et al, 2012;Zhou et al, 2007). Based on clinical findings, bone X-ray examination should be performed first on suspicion of PPD, and the diagnosis can be confirmed through whole exome sequencing (WES).…”

Investigation of Genetic Etiology in Five Turkish Male Patients With Pre-Diagnosed Spondyloepi (Meta) Physeal Dysplasia

“…This mutation was previously reported in the Human Genome Mutation Database-Public Version (HGMD public) with the code CM991252. The c.210C>A mutation has been reported from several countries, including Italy, France, Lebanon, Syria, Turkey, Germany, India and Iran (6,9,(14)(15)(16)(17)(18)(19). This mutation accounts for almost 28% of the pathogenic variants associated with PPRD.…”

Exploring and expanding the phenotype and genotype diversity in seven Chinese families with spondylo-epi-metaphyseal dysplasia

“…We reported seven families with SEMD caused by TRPV4 , COL2A1 , CCN6 , SBDS , and ACAN genes in order to explore the relationship between phenotype and genotype of them. Several studies have reported the phenotype–genotype relations of skeletal disorders caused by COL2A1 , COMP , and CCN6 genes ( Barat-Houari et al, 2016a ; Madhuri et al, 2016 ; Liang et al, 2021 ), but we still need more families to prove it, especially Chinese families. Therefore, we summarized the clinical manifestations, radiological data, and molecular features of patients with SEMD, hoping to improve our understanding of Chinese families with SEMD.…”