title: Early severe scoliosis in a patient with atypical progressive pseudorheumatoid dysplasia (PPD): Identification of two WISP3 mutations, one previously unreported.
abstract: Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive disorder characterized by spondyloepiphyseal dysplasia associated with pain and stiffness of multiple joints, enlargement of the interphalangeal joints, normal inflammatory parameters, and absence of extra-skeletal manifestations. Homozygous or compound heterozygous WISP3 mutations cause PPD. We report two siblings from a non-consanguineous Ecuadorian family with a late-onset spondyloepiphyseal dysplasia. Mutation screening was undertaken in the two affected siblings using a customized skeletal dysplasia next generation sequencing (NGS) panel and confirmed by Sanger sequencing. Two compound heterozygous mutations were identified in WISP3 exon 2, c.[190G>A];[197G>A] (p.[(Gly64Arg)];[(Ser66Asn)]) in the two siblings, both of which had been inherited. The p. (Gly64Arg) mutation has not been previously described whilst the p. (Ser66Asn) mutation has been reported in two PPD families. The two siblings presented with atypical PPD, as they presented during late childhood, yet the severity was different between them. The progression was particularly aggressive in the male sibling who suffered severe scoliosis by the age of 13 years. This case reaffirms the clinical heterogeneity of this disorder and the clinical utility of NGS to genetically diagnose skeletal dysplasias, enabling adequate management, monitorization, and genetic counseling. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Pediatrics, Hospital Universitario Infanta Leonor, Madrid, Spain.|Multidisciplinary Unit for Skeletal dysplasias (UMDE), Hospital Universitario La Paz, Madrid, Spain.|Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.
authors.forename: Lucia Sentchordi
authors.initials: LS
authors.lastname: Montané
authors.affiliation: Department of Traumatology and Orthopedics, Hospital Universitario Infanta Leonor, Madrid, Spain.
authors.forename: Oliver R
authors.initials: OR
authors.lastname: Marín
authors.affiliation: Multidisciplinary Unit for Skeletal dysplasias (UMDE), Hospital Universitario La Paz, Madrid, Spain.|Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.
authors.forename: Carlos I
authors.initials: CI
authors.lastname: Rivera-Pedroza
authors.affiliation: Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Vallespín
authors.affiliation: Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.
authors.forename: Ángela
authors.initials: Á
authors.lastname: Del Pozo
authors.affiliation: Multidisciplinary Unit for Skeletal dysplasias (UMDE), Hospital Universitario La Paz, Madrid, Spain.|Institute of Medical and Molecular Genetics (INGEMM), Hospital Universitario La Paz, Universidad Autónoma de Madrid, IdiPAZ, Madrid, Spain.|Centro de Investigación Biomédica en Enfermedades Raras (CIBERER), Instituto Carlos III, Madrid, Spain.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Heath
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D019943:Amino Acid Substitution; D055511:CCN Intercellular Signaling Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007592:Joint Diseases / Q000151:congenital* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009154:Mutation; D010641:Phenotype; D011859:Radiography; D012600:Scoliosis / Q000175:diagnosis* / Q000235:genetics*; D012720:Severity of Illness Index; D035781:Siblings; D055815:Young Adult
chemical_list: D055511:CCN Intercellular Signaling Proteins; C400081:CCN6 protein, human
keywords: NGS; PPD; WISP3; progressive pseudorheumatoid dysplasia; scoliosis; skeletal dysplasias