Disrupted auto-regulation of the spliceosomal gene SNRPB causes cerebro–costo–mandibular syndrome
نویسندگان
چکیده
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.
منابع مشابه
Cerebro-costo-mandibular syndrome: Report of two cases
Cerebro-costo-mandibular syndrome (CCMS) is a rare syndrome that includes a constellation of mandibular hypoplasia and posterior rib defects as its basic features. Additional features can include hearing loss, tracheal cartilage abnormalities, scoliosis, elbow hypoplasia, and spina bifida. Here we report two cases of CCMS and discuss the reported long-term outcome of the disease.
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The cerebro-costo-mandibular syndrome is characterized by cerebral maldevelopment or malfunction or both, costal deficiencies, and micrognathia. Cleft palate and glossoptosis are frequently present and contribute to the common presenting sign, neonatal respiratory distress. Intrauterine and postnatal growth retardation are common. Familial cases are rare and the mode of transmission is uncertai...
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