Ubiquitin Ligases of the N-End Rule Pathway: Assessment of Mutations in UBR1 That Cause the Johanson-Blizzard Syndrome
2011

Mutations in UBR1 and Johanson-Blizzard Syndrome

Sample size: 3 publication 10 minutes Evidence: moderate

Author Information

Author(s): Hwang Cheol-Sang, Sukalo Maja, Batygin Olga, Addor Marie-Claude, Brunner Han, Aytes Antonio Perez, Mayerle Julia, Song Hyun Kyu, Varshavsky Alexander, Zenker Martin

Primary Institution: California Institute of Technology

Hypothesis

The study investigates the role of UBR1 mutations in causing Johanson-Blizzard Syndrome (JBS).

Conclusion

The study confirms that specific missense mutations in UBR1 are associated with milder variants of Johanson-Blizzard Syndrome.

Supporting Evidence

  • Missense mutations in UBR1 were found in patients with milder forms of JBS.
  • Patients with severe JBS had mutations that likely abolished UBR1 activity.
  • Yeast models demonstrated varying activities of UBR1 mutants corresponding to patient mutations.

Takeaway

Some kids with Johanson-Blizzard Syndrome have milder symptoms because their UBR1 gene has small changes instead of big ones that completely stop it from working.

Methodology

The study involved analyzing UBR1 mutations in patients with Johanson-Blizzard Syndrome and testing the effects of these mutations in yeast models.

Limitations

The study is limited by the small sample size and the focus on specific mutations without exploring the full range of UBR1 mutations.

Participant Demographics

Patients were sporadic cases born to healthy unrelated parents of European origin.

Digital Object Identifier (DOI)

10.1371/journal.pone.0024925

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