Mutations of CEP83 cause infantile nephronophthisis and intellectual disability

Marion Failler, Heon Yung Gee, Pauline Krug, Kwangsic Joo, Jan Halbritter, Lilya Belkacem, Emilie Filhol, Jonathan D. Porath, Daniela A. Braun, Markus Schueler, Amandine Frigo, Olivier Alibeu, Cécile Masson, Karine Brochard, Bruno Hurault De Ligny, Robert Novo, Christine Pietrement, Hulya Kayserili, Rémi Salomon, Marie Claire GublerEdgar A. Otto, Corinne Antignac, Joon Kim, Alexandre Benmerah, Friedhelm Hildebrandt, Sophie Saunier

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42 Citations (Scopus)


Ciliopathies are a group of hereditary disorders associated with defects in cilia structure and function. The distal appendages (DAPs) of centrioles are involved in the docking and anchoring of the mother centriole to the cellular membrane during ciliogenesis. The molecular composition of DAPs was recently elucidated and mutations in two genes encoding DAPs components (CEP164/NPHP15, SCLT1) have been associated with human ciliopathies, namely nephronophthisis and orofaciodigital syndrome. To identify additional DAP components defective in ciliopathies, we independently performed targeted exon sequencing of 1,221 genes associated with cilia and 5 known DAP protein-encoding genes in 1,255 individuals with a nephronophthisis-related ciliopathy. We thereby detected biallelic mutations in a key component of DAP-encoding gene, CEP83, in seven families. All affected individuals had early-onset nephronophthisis and four out of eight displayed learning disability and/or hydrocephalus. Fibroblasts and tubular renal cells from affected individuals showed an altered DAP composition and ciliary defects. In summary, we have identified mutations in CEP83, another DAP-component-encoding gene, as a cause of infantile nephronophthisis associated with central nervous system abnormalities in half of the individuals.

Original languageEnglish
Pages (from-to)905-914
Number of pages10
JournalAmerican Journal of Human Genetics
Issue number6
Publication statusPublished - 2014 Jun 5

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)

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    Failler, M., Gee, H. Y., Krug, P., Joo, K., Halbritter, J., Belkacem, L., Filhol, E., Porath, J. D., Braun, D. A., Schueler, M., Frigo, A., Alibeu, O., Masson, C., Brochard, K., Hurault De Ligny, B., Novo, R., Pietrement, C., Kayserili, H., Salomon, R., ... Saunier, S. (2014). Mutations of CEP83 cause infantile nephronophthisis and intellectual disability. American Journal of Human Genetics, 94(6), 905-914.