Mutations in SNRPB, Encoding Components of the Core Splicing Machinery, Cause Cerebro-Costo-Mandibular Syndrome

作者：Bacrot Severine; Doyard Mathilde; Huber Celine; Alibeu Olivier; Feldhahn Niklas; Lehalle Daphne; Lacombe Didier; Marlin Sandrine; Nitschke Patrick; Petit Florence; Vazquez Marie Paule; Munnich Arnold; Cormier Daire Valerie^*

来源：Human Mutation, 2015, 36(2): 187-190.

DOI：10.1002/humu.22729

• SNRPB
• cerebro-costo-mandibular syndrome
• alternative splicing
• spliceosome
• NMD

Cerebro-costo-mandibular syndrome (CCMS) is a developmental disorder characterized by the association of Pierre Robin sequence and posterior rib defects. Exome sequencing and Sanger sequencing in five unrelated CCMS patients revealed five heterozygous variants in the small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) gene. This gene includes three transcripts, namely transcripts 1 and 2, encoding components of the core spliceosomal machinery (SmB and SmB) and transcript 3 undergoing nonsense-mediated mRNA decay. All variants were located in the premature termination codon (PTC)-introducing alternative exon of transcript 3. Quantitative RT-PCR analysis revealed a significant increase in transcript 3 levels in leukocytes of CCMS individuals compared to controls. We conclude that CCMS is due to heterozygous mutations in SNRPB, enhancing inclusion of a SNRPB PTC-introducing alternative exon, and show that this developmental disease is caused by defects in the splicing machinery. Our finding confirms the report of SNRPB mutations in CCMS patients by Lynch et al. (2014) and further extends the clinical and molecular observations.

• 出版日期2015-2