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2.  Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro–costo–mandibular syndrome 
Nature Communications  2014;5:4483.
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.
Cerebro–costo–mandibular syndrome, CCMS, is a severe human multiple malformation disorder. Here, the authors report that mutations in SNRPB disrupt the normal regulation of alternative splicing at this gene, and in so doing, may be responsible for the development of CCMS.
doi:10.1038/ncomms5483
PMCID: PMC4109005  PMID: 25047197

Results 1-2 (2)