title: 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.
abstract: 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.
authors.affiliation: Unité de Génétique Médicale, Laboratoire de Biologie Moléculaire et Cytogénétique, Faculté de Médecine, Université Saint-Joseph, Beirut, Lebanon.
authors.forename: Valérie
authors.initials: V
authors.lastname: Delague
authors.forename: Eliane
authors.initials: E
authors.lastname: Chouery
authors.forename: Sandra
authors.initials: S
authors.lastname: Corbani
authors.forename: Ismat
authors.initials: I
authors.lastname: Ghanem
authors.forename: Suhail
authors.initials: S
authors.lastname: Aamar
authors.forename: Judith
authors.initials: J
authors.lastname: Fischer
authors.forename: Ephrat
authors.initials: E
authors.lastname: Levy-Lahad
authors.forename: J Andoni
authors.initials: JA
authors.lastname: Urtizberea
authors.forename: André
authors.initials: A
authors.lastname: Mégarbané
mesh_terms: D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000235:genetics* / Q000473:pathology; D001483:Base Sequence; D055511:CCN Intercellular Signaling Proteins; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004252:DNA Mutational Analysis / Q000379:methods; D005192:Family Health; D005260:Female; D018703:Founder Effect; D005602:France; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics*; D008297:Male; D008877:Middle East / Q000208:ethnology; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human; D018969:Insulin-Like Growth Factor Binding Proteins; D009363:Neoplasm Proteins