Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice
2011

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic Syndrome in Humans and Mice

Sample size: 14 publication 10 minutes Evidence: high

Author Information

Author(s): Rainger Joe, van Beusekom Ellen, Ramsay Jacqueline K., McKie Lisa, Al-Gazali Lihadh, Pallotta Rosanna, Saponari Anita, Branney Peter, Fisher Malcolm, Morrison Harris, Bicknell Louise, Gautier Philippe, Perry Paul, Sokhi Kishan, Sexton David, Bardakjian Tanya M., Schneider Adele S., Elcioglu Nursel, Ozkinay Ferda, Koenig Rainer, Mégarbané Andre, Semerci C. Nur, Khan Ayesha, Zafar Saemah, Hennekam Raoul, Sousa Sérgio B., Ramos Lina, Garavelli Livia, Furga Andrea Superti, Wischmeijer Anita, Jackson Ian J., Gillessen-Kaesbach Gabriele, Brunner Han G., Wieczorek Dagmar, van Bokhoven Hans, FitzPatrick David R.

Primary Institution: Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, United Kingdom

Hypothesis

Are mutations in the SMOC1 gene responsible for Ophthalmo-Acromelic Syndrome?

Conclusion

Mutations in the SMOC1 gene are identified as a significant cause of Ophthalmo-Acromelic Syndrome, affecting both humans and mice.

Supporting Evidence

  • Eight different mutations in the SMOC1 gene were identified in unrelated individuals with Ophthalmo-Acromelic Syndrome.
  • Six of these mutations are predicted to completely abolish SMOC-1 function.
  • Mouse models with reduced SMOC1 function exhibit similar limb malformations to those seen in human patients.
  • Partial loss of SMOC-1 results in a convincing phenocopy of the human disease.

Takeaway

This study found that a gene called SMOC1 is broken in some people and mice, which leads to problems with their eyes and limbs.

Methodology

The study used homozygosity mapping and targeted mutation analysis to identify mutations in the SMOC1 gene in affected families.

Limitations

Some families with typical OAS did not have identifiable SMOC1 mutations, suggesting other genetic factors may be involved.

Participant Demographics

The study included eight unrelated families with Ophthalmo-Acromelic Syndrome.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pgen.1002114

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