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MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome

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Abstract

Meckel syndrome (MKS) is a severe fetal developmental disorder reported in most populations. The clinical hallmarks are occipital meningoencephalocele, cystic kidney dysplasia, fibrotic changes of the liver and polydactyly. Here we report the identification of a gene, MKS1, mutated in MKS families linked to 17q. Mks1 expression in mouse embryos, as determined by in situ hybridization, agrees well with the tissue phenotype of MKS. Comparative genomics and proteomics data implicate MKS1 in ciliary functions.

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Figure 1: In situ hybridization analysis of Mks1 expression in mouse embryos.

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Acknowledgements

We thank the families for participating in the study and thank all the scientists, clinicians and genetic counselors for their collaboration in the MKS project. The work was supported by a Finnish Cultural Foundation grant to M. Kyttälä and an Academy of Finland grant to M. Kestilä. L. Peltonen was supported by a grant from the US National Institutes of Health, a grant from the Center of Excellence in Disease Genetics (the Academy of Finland) and the Biocentrum Helsinki.

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Authors and Affiliations

  1. Department of Molecular Medicine, National Public Health Institute, Helsinki, FI-00251, Finland

    Mira Kyttälä, Jonna Tallila, Outi Kopra, Leena Peltonen & Marjo Kestilä

  2. Department of Medical Genetics, University of Helsinki, Helsinki, FI-00014, Finland

    Mira Kyttälä & Leena Peltonen

  3. Department of Medical Genetics, Väestöliitto, Helsinki, FI-00101, Finland

    Riitta Salonen

  4. Neuroscience Center, University of Helsinki, Helsinki, FI-00014, Finland

    Outi Kopra

  5. Institute of Human Genetics, University Hospital, Mainz, D-55101, Germany

    Nicolai Kohlschmidt

  6. Department of Medicine, Helsinki University Hospital, Helsinki, FI-00029, Finland

    Paulina Paavola-Sakki

  7. The Broad Institute of Harvard and the Massachusetts Institute of Technology, Boston, 02139, Massachusetts, USA

    Leena Peltonen

Authors
  1. Mira Kyttälä
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  2. Jonna Tallila
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  3. Riitta Salonen
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  4. Outi Kopra
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  5. Nicolai Kohlschmidt
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  6. Paulina Paavola-Sakki
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  7. Leena Peltonen
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  8. Marjo Kestilä
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Corresponding author

Correspondence to Leena Peltonen.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Haplotypes in Finnish MKS chromosomes, the critical chromosomal region and the genomic structure of MKS1. (PDF 205 kb)

Supplementary Fig. 2

The mutation analysis of MKS1. (PDF 217 kb)

Supplementary Fig. 3

MKS1 peptide sequence comparison between species. (PDF 380 kb)

Supplementary Methods (PDF 189 kb)

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Kyttälä, M., Tallila, J., Salonen, R. et al. MKS1, encoding a component of the flagellar apparatus basal body proteome, is mutated in Meckel syndrome. Nat Genet 38, 155–157 (2006). https://doi.org/10.1038/ng1714

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  • DOI: https://doi.org/10.1038/ng1714

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