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Mainzer-Saldino syndrome is a ciliopathy caused by mutations in the IFT140 gene


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Submitted on 16 Nov 2012

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Mainzer-Saldino syndrome is a ciliopathy caused by

mutations in the IFT140 gene

Isabelle Perrault, Sophie Saunier, Sylvain Hanein, Emile Filhol, Albane Bizet,

Felicity Collins, Mustafa Salih, Eduardo Silva, Véronique Baudouin, Machteld

Oud, et al.

To cite this version:

Isabelle Perrault, Sophie Saunier, Sylvain Hanein, Emile Filhol, Albane Bizet, et al.. Mainzer-Saldino

syndrome is a ciliopathy caused by mutations in the IFT140 gene. First International Cilia in

Devel-opment and Disease Scientific Conference, pp.O28. �inserm-00752958�



Open Access

Mainzer-Saldino syndrome is a ciliopathy caused

by mutations in the

IFT140 gene

I Perrault


, S Saunier


, S Hanein


, E Filhol


, A Bizet


, F Collins


, M Salih


, E Silva


, V Baudouin


, M Oud



N Shannon


, M Le Merrer


, C Pietrement


, P Beales


, H Arts


, A Munnich


, J Kaplan


, C Antignac



V Cormier Daire


, JM Rozet


From First International Cilia in Development and Disease Scientific Conference (2012)

London, UK. 16-18 May 2012


Ciliopathies is an emerging class of genetic disorders due to altered cilia assembly, maintenance or function. Syndro-mic ciliopathies affecting bone development have been classified as skeletal ciliopathies. Mutations in genes encoding components of the intraflagellar transport (IFT) complex A, that drives retrograde ciliary transport, are a major cause of skeletal ciliopathies. Mainzer-Saldino syn-drome (MSS) is a rare disorder characterized by phalan-geal cone-shaped epiphyses, chronic renal failure and early-onset severe retinal dystrophy.

Methods and results

We collected 16 families presenting three diagnostic cri-teria of MSS. Through ciliome re-sequencing combined to Sanger sequencing, we identified IFT140 mutations in seven MSS families. The effect of the mutations on IFT140 localization was assessed using flagged-IFT140 mutant proteins which showed a partial to nearly complete loss of basal body localization associated with an increase of cyto-plasm staining while the wild-type Flagged-IFT140 protein predominantly localized to the basal bodies in RPE1 cells. To assess the impact ofIFT140 mutations on ciliogenesis, abundance and morphology of primary cilia were studied in cultured fibroblasts of patients and detected absent cilia in a high proportion of patient cells compared to controls. Ciliary localization of anterograde IFTs were altered in MSS patient fibroblasts supporting the pivotal role of IFT140 in proper development and function of ciliated cells.


Here we report on compound heterozygosity or homozyg-osity forIFT140 mutations in seven MSS families. After Sensenbrenner and Jeune syndromes, MSS is the ultimate skeletal ciliopathy ascribed to IFT disorganization.

Author details

1INSERM U781 & Department of Genetics, Paris Descartes University, France. 2INSERM, U983, Paris Descartes University, France.3Department of Clinical

Genetics,Westmead Hospital, Sydney, Australia.4Division of Pediatric Neurology, King Khalid University Hospital, Riyadh, Saudi Arabia.5Department of

Ophthalmology, Coimbra University Hospital, Portugal.6Department of Nephrology, CHU Robert Debré, Paris, France.7Department of Human Genetics,

Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.

8Clinical Genetics Service, City Hospital, Nottingham, UK.9Department of

Pediatry, American Memorial Hospital, CHU Reims, France.10Molecular Medicine Unit, University College London (UCL) Institute of Child Health , UK.

Published: 16 November 2012


Cite this article as: Perrault et al.: Mainzer-Saldino syndrome is a ciliopathy caused by mutations in theIFT140 gene. Cilia 2012 1(Suppl 1): O28.

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Submit your manuscript at www.biomedcentral.com/submit * Correspondence: isabelle.perrault@inserm.fr

1INSERM U781 & Department of Genetics, Paris Descartes University, France

Full list of author information is available at the end of the article Perraultet al. Cilia 2012, 1(Suppl 1):O28


© 2012 Perrault et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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