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Mutation in IFT80 in a fetus with the phenotype of Verma-Naumoff provides molecular evidence for Jeune-Verma-Naumoff dysplasia spectrum
  1. Denise P Cavalcanti1,2,
  2. Celine Huber2,
  3. Kim-Hanh Le Quan Sang2,
  4. Geneviève Baujat2,
  5. Felicity Collins3,
  6. Anne-Lise Delezoide4,
  7. Nathalie Dagoneau2,
  8. Martine Le Merrer2,
  9. Jelena Martinovic5,
  10. Marcos Fernando S Mello6,
  11. Michel Vekemans2,
  12. Arnold Munnich2,
  13. Valerie Cormier-Daire2
  1. 1Perinatal Genetic Program, Department of Medical Genetic, FCM, UNICAMP, Campinas, São Paulo, Brazil
  2. 2Department of Genetics, INSERM U 781, Université Paris Descartes, AP-HP, Hôpital Necker Enfants Malades, Paris, France
  3. 3Western Sydney Genetics Program, Department of Clinical Genetics, Children's Hospital at Westmead, Sydney, Australia
  4. 4Service de Biologie de Développement, Université Paris Diderot, Hôpital Robert Debré, Paris, France
  5. 5Unit of Fetal Pathology, Department of Histo-Embryology and Cytogenetics, Hôpital Necker-Enfants Malades, Paris, France
  6. 6Department of Pathology, FCM, UNICAMP, Campinas, São Paulo, Brazil
  1. Correspondence to Prof Denise P Cavalcanti, Programa de Genética Perinatal, Depto. de Genética Médica, FCM, UNICAMP, CP 6111, 13081-970, Campinas, SP Brazil; denisepc{at}unicamp.br denisepcavalcanti{at}gmail.com

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 dysplasias also used to be classified in the SRP group. Recently, mutations in a gene encoding a protein involved in intraflagellar transport, IFT80, have been identified in 3/39 patients with Jeune dysplasia but no extraskeletal manifestation.

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

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

Conclusions The findings show that mutations in IFT80 can also be responsible for a lethal form of SRP and provide the molecular basis for the Jeune-Verma-Naumoff dysplasia spectrum.

  • Short rib-polydactyly dysplasia
  • IFT80
  • ciliopathy
  • Verma-Naumoff dysplasia
  • Jeune dysplasia
  • diagnosis
  • genetics
  • clinical genetics
  • molecular genetics

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Footnotes

  • Funding This work was supported by grants from Fapesp (98/16006-6), CAPES (0603/08-2) and PHRC (AOM06031).

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of UNICAMP, Campinas, SP, Brazil, Hôpital Necker, Paris, France, Hôpital Robert Debre, Paris, France and Children's Hospital at Westmead, Sydney, Australia.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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