Novel SMC1A frameshift mutations in children with developmental delay and epilepsy

Jessica H.R. Goldstein, Thipwimol Tim-aroon, Joseph Shieh, Michelle Merrill, Kristin K. Deeb, Shulin Zhang, Nancy E. Bass, Jirair K. Bedoyan

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Cornelia de Lange syndrome (CdLS) is a rare dominantly inherited genetic multisystem developmental condition with considerable phenotypic and allelic heterogeneity. Missense and in-frame deletions within the SMC1A gene can be associated with epilepsy and milder craniofacial features. We report two females who presented with developmental delay and developed isolated medically refractory seizures with unrevealing initial laboratory, imaging and genetic evaluations. Whole exome sequencing (WES) analyses were performed and were instrumental in uncovering the genetic etiology for their conditions. WES identified two novel de novo heterozygous frameshift mutations in the SMC1A gene [c.2853_2856delTCAG (p.Ser951Argfs*12) and c.3549_3552dupGGCC (p.Ile1185Glyfs*23)]. We also observed marked skewing of X-inactivation in one patient. The individual with the p.Ser951Argfs*12 mutation represents an extreme on the CdLS phenotypic spectrum, with prominent neurological involvement of severe developmental delay and refractory epilepsy, with mild craniofacial features. Both individuals eventually had incomplete clinical responses to therapy with valproic acid. We review previous reports of SMC1A mutations with epilepsy. SMC1A should be included in clinical gene panels for early infantile and early childhood epileptic encephalopathy.

Original languageEnglish (US)
Pages (from-to)562-568
Number of pages7
JournalEuropean Journal of Medical Genetics
Issue number10
StatePublished - Oct 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 Elsevier Masson SAS.


  • Cornelia de Lange syndrome
  • SMC1A
  • Status epilepticus
  • Whole exome sequencing


Dive into the research topics of 'Novel SMC1A frameshift mutations in children with developmental delay and epilepsy'. Together they form a unique fingerprint.

Cite this