Clinical and molecular characterization in a cohort of patients with progressive pseudorheumatoid dysplasia

Abstract Progressive pseudorheumatoid dysplasia (PPRD), a rare autosomal recessive syndrome, is a type of skeletal dysplasia associated with pain, stiffness, swelling of multiple joints, and the absence of destructive changes. PPRD occurs due to loss of function pathogenic variants in WISP3 ( CCN6 ) gene, located on chromosome 6q22. In this study, 23 unrelated Egyptian PPRD patients were clinically diagnosed based on medical history, physical and radiological examinations, and laboratory investigations. Sequencing of the whole WISP3 ( CCN6 ) exons and introns boundaries was carried out for all patients. A total of 11 different sequence variations were identified in the WISP3 ( CCN6 ) gene, five of them were new pathogenic variants: the NM_003880.3: c.80T>A (p.L27*), c.161delG (p.C54fs*12), c.737T>C (p.Leu246Pro), c.347‐1G>A (IVS3‐1G>A), and c.376C>T (p.Q126*). The results of this study expand the spectrum of WISP3 ( CCN6 ) pathogenic variants associated with PPRD. Clinical and genetic analysis is important for proper genetic counseling to curb this rare disorder in the families.