Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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

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.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

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

References

  1. Paavola, P., Salonen, R., Weissenbach, J. & Peltonen, L. The locus for Meckel syndrome with multiple congenital anomalies maps to chromosome 17q21-q24. Nat. Genet. 11, 213–215 (1995).

    Article  CAS  Google Scholar 

  2. Roume, J. et al. A gene for Meckel syndrome maps to chromosome 11q13. Am. J. Hum. Genet. 63, 1095–1101 (1998).

    Article  CAS  Google Scholar 

  3. Morgan, N.V. et al. A novel locus for Meckel-Gruber syndrome, MKS3, maps to chromosome 8q24. Hum. Genet. 111, 456–461 (2002).

    Article  CAS  Google Scholar 

  4. Hentges, K.E., Kyttala, M., Justice, M.J. & Peltonen, L. Comparative physical maps of the human and mouse Meckel syndrome critical regions. Mamm. Genome 15, 252–264 (2004).

    Article  CAS  Google Scholar 

  5. Swoboda, P., Adler, H.T. & Thomas, J.H. The RFX-type transcription factor DAF-19 regulates sensory neuron cilium formation in C. elegans. Mol. Cell 5, 411–421 (2000).

    Article  CAS  Google Scholar 

  6. Efimenko, E. et al. Analysis of xbx genes in C. elegans. Development 132, 1923–1934 (2005).

    Article  CAS  Google Scholar 

  7. Li, J.B. et al. Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell 117, 541–552 (2004).

    Article  CAS  Google Scholar 

  8. Keller, L.C., Romijn, E.P., Zamora, I., Yates, J.R. III & Marshall, W.F. Proteomic analysis of isolated chlamydomonas centrioles reveals orthologs of ciliary-disease genes. Curr. Biol. 15, 1090–1098 (2005).

    Article  CAS  Google Scholar 

  9. Kramer-Zucker, A.G. et al. Cilia-driven fluid flow in the zebrafish pronephros, brain and Kupffer's vesicle is required for normal organogenesis. Development 132, 1907–1921 (2005).

    Article  CAS  Google Scholar 

  10. Nauli, S.M. et al. Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nat. Genet. 33, 129–137 (2003).

    Article  CAS  Google Scholar 

  11. Blacque, O.E. et al. Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev. 18, 1630–1642 (2004).

    Article  CAS  Google Scholar 

  12. Pazour, G.J. et al. Chlamydomonas IFT88 and its mouse homologue, polycystic kidney disease gene tg737, are required for assembly of cilia and flagella. J. Cell Biol. 151, 709–718 (2000).

    Article  CAS  Google Scholar 

  13. Supp, D.M., Witte, D.P., Potter, S.S. & Brueckner, M. Mutation of an axonemal dynein affects left-right asymmetry in inversus viscerum mice. Nature 389, 963–966 (1997).

    Article  CAS  Google Scholar 

  14. Okada, Y. et al. Abnormal nodal flow precedes situs inversus in iv and inv mice. Mol. Cell 4, 459–468 (1999).

    Article  CAS  Google Scholar 

  15. Salonen, R. The Meckel syndrome: clinicopathological findings in 67 patients. Am. J. Med. Genet. 18, 671–689 (1984).

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Leena Peltonen.

Ethics declarations

Competing interests

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)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing