Magic™ Anti-SMC1A (Phospho S957) polyclonal antibody

SMC1A variants causing Cornelia de Lange syndrome (CdLS) produce another phenotype characterized by moderate to severe neurological impairment and severe early-onset epilepsy without morphological characteristics of CdLS. The patients are all female and have truncation mutations in SMC1A. The epilepsy also follows a characteristic clinical course with pharmaco-resistant cluster seizures since infancy, mimicking that of PCDH19-related epilepsy. We report here that a missense variant of the SMC1A gene affecting a daughter (proband) and her mother caused similar phenotypes of early-onset (2 years and 1 month of age) and late-onset (12 years of age) epilepsy, respectively. Both patients lacked the morphological characteristics of CdLS, and had severe and moderate intellectual disability, respectively. The cluster seizures were characteristic, occurring approximately every 2-4 weeks (interval; mean +/- SD: 20.2 +/- 8.3 days) at the peak of the clinical course, especially in the proband. Thus, SMC1A-related encephalopathy is caused not only by truncation mutations but also by missense variants of the SMC1A gene. The periodicity of cluster seizures mimicking that of PCDH19-related epilepsy may characterize SMC1A-related encephalopathy.

SMC1A (structural maintenance of chromosomes 1A), which encodes a structural subunit of the cohesin protein complex, is necessary for the process of sister chromatid cohesion during the cell cycle. Mutation and deregulation of SMC1A are highly relevant to diverse human diseases, including Cornelia de Lange syndrome and malignant carcinomas. In order to further investigate the role of SMC1A in the oncogenesis of lung cancer, SMC1A-specific short hairpin RNA (shRNA)-expressing lentivirus (Lv-shSMC1A) was constructed and used to infect A549 and H1299 cells. SMC1A mRNA and protein expression levels were downregulated in A549 and H1299 cells as demonstrated by real-time PCR and western blot assays. We found that SMC1A inhibition resulted in significantly impaired proliferation and colony formation as well as reduced invasiveness of tumor cells. Notably, Lv-shSMC1A-infected cancer cells exhibited a greater proportion of cells in the G0/G1 phase, but a lower proportion of S phase cells, compared to the parent or Lv-shCon infected cancer cells. Moreover, a greater proportion of sub-G1 apoptotic cells was observed in Lv-shSMC1A-infected cells. These results suggest that SMC1A is a novel proliferation regulator that promotes the growth of lung cancer cells, and that down-regulation of SMC1A expression induces growth suppression of A549 and H1299 cells via G1/S cell cycle phase arrest and apoptosis pathways. Therefore, SMC1A may serve as a new molecular target for lung cancer therapy.