Molecular study of WISP3 in nine families originating from the Middle-East and presenting with progressive pseudorheumatoid dysplasia:: Identification of two novel mutations, and description of a founder effect

Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive syndrome characterized by the presence of spondyloepiphyseal dysplasia associated with pain, stiffness, and swelling of multiple joints, osteoporosis, and the absence of destructive bone changes. The disorder is caused by mutations of the WISP3 gene located on chromosome 6q22. We hereby report the molecular study of the WISP3 gene in nine unrelated consanguineous families originating from the Middle-East: three from Lebanon, five from Syria, and one from Palestinian Bedouin descent, all affected with PPD. Five different sequence variations were identified in the WISP3 gene, two of them being new mutations: the c.589G -> C transversion at codon 197, responsible for a splicing defect (A197fsX201); and the c.536_537delGT deletion (C179fsX), both in exon 3. In all other families, the affected patients were homozygous for a previously described nonsense mutation, namely c.156C -> A (C52X). Interestingly, in the latter families, the C52X mutation was always found associated with a novel c.248G -> A (G83E) variation, suggesting the existence of a founder effect. (c) 2005 Wiley-Liss.