title: Early-onset encephalopathy with epilepsy associated with a novel splice site mutation in SMC1A.
abstract: We report on the clinical and molecular characterization of a female patient with early-onset epileptic encephalopathy, who was found to carry a de novo novel splice site mutation in SMC1A. This girl shared some morphologic and anthropometric traits described in patients with clinical diagnosis of Cornelia de Lange syndrome and with SMC1A mutation but also has severe encephalopathy with early-onset epilepsy. In addition, she had midline hand stereotypies and scoliosis leading to the misdiagnosis of a Rett overlap syndrome. Molecular studies found a novel de novo splice site mutation (c.1911 + 1G > T) in SMC1A. This novel splice mutation was associated with an aberrantly processed mRNA that included intron 11 of the gene. Moreover, quantitative approach by RT-PCR showed a severe reduction of the SMC1A transcript suggesting that this aberrant transcript may be unstable and degraded. Taken together, our data suggest that the phenotype may be due to a loss-of-function of SMC1A in this patient. Our findings suggest that loss-of-function mutations of SMC1A may be associated with early-onset encephalopathy with epilepsy.
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lebrun
authors.affiliation: Department of Pediatrics, Pediatric Neurology and Neurorehabilitation Unit, Lausanne University Hospital, Switzerland.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lebon
authors.affiliation: Department of Pediatrics, Pediatric Neurology and Neurorehabilitation Unit, Lausanne University Hospital, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Jeannet
authors.affiliation: Département de Pédiatrie, Faculté de médecine, Université de Montréal, CHU Sainte Justine, Montreal, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Jacquemont
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Billuart
authors.affiliation: Inserm, Institut Cochin, Paris, France.|Cnrs, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris, France.|Assistance Publique - Hôpitaux de Paris, Groupe Universitaire Paris Centre, Site Cochin, Laboratoire de Biochimie et Génétique Moléculaire, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D017668:Age of Onset; D001927:Brain Diseases / Q000175:diagnosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D003635:De Lange Syndrome / Q000175:diagnosis / Q000235:genetics*; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011379:Prognosis; D022821:RNA Splice Sites / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098550:Structural Maintenance of Chromosome Protein 1
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D022821:RNA Splice Sites; D012333:RNA, Messenger; D000098550:Structural Maintenance of Chromosome Protein 1
keywords: SMC1A mutations; cornelia de lange syndrome; epileptic encephalopathy; splice mutation