Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro-costo-mandibular syndrome

Danielle C. Lynch, Timothée Revil, Jeremy Schwartzentruber, Elizabeth J. Bhoj, A. Micheil Innes, Ryan E. Lamont, Edmond G. Lemire, Bernard N. Chodirker, Juliet P. Taylor, Elaine H. Zackai, D. Ross McLeod, Edwin P. Kirk, Julie Hoover-Fong, Leah Fleming, Ravi Savarirayan, Kym Boycott, Alex MacKenzie, Jacek Majewski, Michael Brudno, Dennis BulmanDavid Dyment, Loydie A. Jerome-Majewska, Jillian S. Parboosingh, Francois P. Bernier

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Elucidating the function of highly conserved regulatory sequences is a significant challenge in genomics today. Certain intragenic highly conserved elements have been associated with regulating levels of core components of the spliceosome and alternative splicing of downstream genes. Here we identify mutations in one such element, a regulatory alternative exon of SNRPB as the cause of cerebro-costo-mandibular syndrome. This exon contains a premature termination codon that triggers nonsense-mediated mRNA decay when included in the transcript. These mutations cause increased inclusion of the alternative exon and decreased overall expression of SNRPB. We provide evidence for the functional importance of this conserved intragenic element in the regulation of alternative splicing and development, and suggest that the evolution of such a regulatory mechanism has contributed to the complexity of mammalian development.

Original languageEnglish (US)
Article number4483
JournalNature communications
StatePublished - Jul 22 2014

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)


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