Phenotypic spectrum and prevalence of INPP5E mutations in Joubert Syndrome and related disorders

Lorena Travaglini, Francesco Brancati, Jennifer Silhavy, Miriam Iannicelli, Elizabeth Nickerson, Nadia Elkhartoufi, Eric Scott, Emily Spencer, Stacey Gabriel, Sophie Thomas, Bruria Ben-Zeev, Enrico Bertini, Eugen Boltshauser, Malika Chaouch, Maria Roberta Cilio, Mirjam M. De Jong, Hulya Kayserili, Gonul Ogur, Andrea Poretti, Sabrina SignoriniGraziella Uziel, Maha S. Zaki, Colin Johnson, Tania Attié-Bitach, Joseph G. Gleeson, Enza Maria Valente*, L. Ali Pacha, A. Zankl, R. Leventer, P. Grattan-Smith, A. Janecke, J. Koch, M. Freilinger, M. D'Hooghe, Y. Sznajer, C. Vilain, R. Van Coster, L. Demerleir, K. Dias, C. Moco, A. Moreira, C. Ae Kim, G. Maegawa, I. Dakovic, D. Loncarevic, V. Mejaski-Bosnjak, D. Petkovic, G. M.H. Abdel-Salam, A. Abdel-Aleem, R. Koul, International JSRD Study Group

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Citations (Scopus)


Joubert syndrome and related disorders (JSRD) are clinically and genetically heterogeneous ciliopathies sharing a peculiar midbrain-hindbrain malformation known as the 'molar tooth sign'. To date, 19 causative genes have been identified, all coding for proteins of the primary cilium. There is clinical and genetic overlap with other ciliopathies, in particular with Meckel syndrome (MKS), that is allelic to JSRD at nine distinct loci. We previously identified the INPP5E gene as causative of JSRD in seven families linked to the JBTS1 locus, yet the phenotypic spectrum and prevalence of INPP5E mutations in JSRD and MKS remain largely unknown. To address this issue, we performed INPP5E mutation analysis in 483 probands, including 408 JSRD patients representative of all clinical subgroups and 75 MKS fetuses. We identified 12 different mutations in 17 probands from 11 JSRD families, with an overall 2.7% mutation frequency among JSRD. The most common clinical presentation among mutated families (7/11, 64%) was Joubert syndrome with ocular involvement (either progressive retinopathy and/or colobomas), while the remaining cases had pure JS. Kidney, liver and skeletal involvement were not observed. None of the MKS fetuses carried INPP5E mutations, indicating that the two ciliopathies are not allelic at this locus.

Original languageEnglish
Pages (from-to)1074-1078
Number of pages5
JournalEuropean Journal of Human Genetics
Issue number10
Publication statusPublished - 2013


  • ciliopathies
  • INPP5E
  • Joubert syndrome and related disorders
  • Meckel syndrome

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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