Overall and allele-specific expression of the SMC1A gene in female Cornelia de Lange syndrome patients and healthy controls

Ilaria Parenti, Davide Rovina, Maura Masciadri, Anna Cereda, Jacopo Azzollini, Chiara Picinelli, Giuseppe Limongelli, Palma Finelli, Angelo Selicorni, Silvia Russo, Cristina Gervasini, Lidia Larizza

Research output: Contribution to journalArticlepeer-review


Cornelia de Lange syndrome (CdLS) is a rare multisystem disorder characterized by facial dysmorphisms, limb anomalies, and growth and cognitive deficits. Mutations in genes encoding subunits (SMC1A, SMC3, RAD21) or regulators (NIPBL, HDAC8) of the cohesin complex account for approximately 65% of clinically diagnosed CdLS cases. The SMC1A gene (Xp11.22), responsible for 5% of CdLS cases, partially escapes X chromosome inactivation in humans and the allele on the inactive X chromosome is variably expressed. In this study, we evaluated overall and allele-specific SMC1A expression. Real-time PCR analysis conducted on 17 controls showed that SMC1A expression in females is 50% higher than in males. Immunoblotting experiments confirmed a 44% higher protein level in healthy females than in males, and showed no significant differences in SMC1A protein levels between controls and patients. Pyrosequencing was used to assess the reciprocal level of allelic expression in six female carriers of different SMC1A mutations and 15 controls who were heterozygous at a polymorphic transcribed SMC1A locus. The two alleles were expressed at a 1:1 ratio in the control group and at a 2:1 ratio in favor of the wild type allele in the test group. Since a dominant negative effect is considered the pathogenic mechanism in SMC1A-defective female patients, the level of allelic preferential expression might be one of the factors contributing to the wide phenotypic variability observed in these patients. An extension of this study to a larger cohort containing mild to borderline cases could enhance our understanding of the clinical spectrum of SMC1A-linked CdLS.

Original languageEnglish
Pages (from-to)973-979
Number of pages7
Issue number7
Publication statusPublished - Apr 22 2014


  • Cornelia de Lange syndrome
  • Differential allelic expression
  • Pyrosequencing
  • Sex-related gene expression
  • SMC1A

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Medicine(all)


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