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Mutation in IFT80 gene in a foetus with a phenotype of Verma-Naumoff provides molecular evidence for the Jeune-Verma-Naumoff dysplasia spectrum
  1. Denise P Cavalcanti (denisepcavalcanti{at}gmail.com)
  1. Universidde Estadual de Campinas (UNICAMP), Brazil
    1. Celine Huber
    1. Universite Paris Descartes, France
      1. Kim-Hanh Sang
      1. Universite Paris Descartes, France
        1. Genevieve Baujat
        1. Universite Paris Descartes, France
          1. Felicity Collins
          1. Children’s Hospital at Westmead, Australia
            1. Anne-Lise Delezoide
            1. Université Paris Diderot, France
              1. Nathalie Dagoneau
              1. Universite Paris Descartes, France
                1. Martine Le Merrer
                1. Universite Paris Descartes, France
                  1. Jelena Martinovic
                  1. Universite Paris Descartes, France
                    1. Marcos Fernando S Mello
                    1. Universidde Estadual de Campinas (UNICAMP), Brazil
                      1. Michel Vekemans
                      1. Universite Paris Descartes, France
                        1. Arnold Munich
                        1. Universite Paris Descartes, France
                          1. Valerie Cormier-Daire
                          1. Universite Paris Descartes, France

                            Abstract

                            Background: The lethal group of short-rib polydactyly (SRP) includes type I (Saldino-Noonan; MIM 263530), type II (Majewski; MIM 263520), type III (Verma-Naumoff; MIM 263510), and type IV (Beemer-Langer; MIM 269860). Jeune and Ellis-van Creveld (EVC) dysplasias also used to be classified in the group of SRP. Recently, mutations in a gene encoding a protein involved in intraflagellar transport (IFT), IFT80, have been identified in 3/39 patients with Jeune dysplasia, but no extraskeletal manifestation.

                            Methods: Due to clinical and radiological similarities between Jeune dysplasia and the other lethal types of SRP we decided to investigate IFT80 in a cohort of foetuses with the lethal forms of SRP (Majewski, Verma-Naumoff, and Beemer-Langer) and cases antenatally diagnosed of Jeune dysplasia. Fifteen foetuses were ascertained to this study. We adopted a double molecular approach. For consanguineous families and for those with recurrent sibs we first performed a haplotype analysis around the gene locus and for the others we directly sequenced all the coding exons of IFT80.

                            Results: Using the haplotype approach for two families, we excluded the IFT80 region as a candidate for them. By direct sequencing of IFT80 in the other 13 cases we found a G-to-C transversion within exon 8 (G241R) in only one SRP case closely related to the type III phenotype.

                            Conclusions: Our findings demonstrate that mutations in IFT80 can also be responsible for a lethal form of SRP and provides the molecular basis for the Jeune-Verma-Naumoff dysplasia spectrum.

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