Progressive pseudorheumatoid dysplasia in North and West Africa: Clinical description in ten patients with mutations of WISP3

Abstract

Progressive pseudorheumatoid dysplasia is a rare autosomal recessive spondyloepiphyseal dysplasia characterized by predominant involvement of articular cartilage with progressive joint stiffness and enlargement in the absence of inflammation. Short stature, joint contractures, gait disturbance, and scoliosis and/or kyphosis, resulting in abnormal posture and significant morbidity are generally seen over time. This condition is caused by mutations of WISP3, a gene located on chromosome 6q21. Ten patients pertaining to 3 families originated from Tunisia, Morocco and Senegal, with progressive pseudorheumatoid dysplasia are described. Three exhibited marked muscle weakness resulting in delayed diagnosis. Genetic studies of WISP3 in these three consanguineous kindred identified two mutations, each at the homozygous state: c.624_625insA (p.C209Mfs*21), also named c.624dupA, in exon 4, in the Tunisian and Senegalese patients, and c.48+2dupT, a splice donor site mutation in intron 1, in the Moroccan patients. The clinical features and the molecular studies of the WISP3 gene are discussed.