2. Academic Validation
  3. De novo GRIN1 mutations: An emerging cause of severe early infantile encephalopathy

De novo GRIN1 mutations: An emerging cause of severe early infantile encephalopathy

  • Eur J Med Genet. 2017 Jun;60(6):317-320. doi: 10.1016/j.ejmg.2017.04.001.
Yoav Zehavi 1,  Hanna Mandel 2,  Arie Zehavi 3,  Muhammad Abu Rashid 4,  Rachel Straussberg 5,  Banan Jabur 4,  Avraham Shaag 6,  Orly Elpeleg 6,  Ronen Spiegel 7
Affiliations

Affiliations

  • 1 Pediatric Department B, Emek Medical Center, Afula, Israel.
  • 2 Institute of Human Genetics and Metabolic Diseases, Galilee Medical Center, Nahariya, Israel.
  • 3 Department of Biotechnology and Food Engineering, Technion, Haifa, Israel.
  • 4 Clalit Health Services, Haifa, Israel.
  • 5 Pediatric Neurology Unit, Schneider Children's Medical Center, Petach Tikva, Israel.
  • 6 Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
  • 7 Pediatric Department B, Emek Medical Center, Afula, Israel; Rappaport School of Medicine, Technion, Haifa, Israel. Electronic address: [email protected].
PMID: 28389307 DOI: 10.1016/j.ejmg.2017.04.001
Abstract

De novo GRIN1 mutations have recently been shown to cause severe intellectual disability, hypotonia, hyperkinetic and stereotyped movements, and epilepsy. We report two new cases of severe early onset encephalopathy associated with hyperkinetic and oculogyric-like movements, caused by mutations in the GRIN1 gene; both were identified by whole exome sequencing. One of the patients harbored the novel mutation p.Ser688Tyr and the other patient harbored the p.Gly827Arg mutation, which was previously reported in three patients. In silico studies suggested that the p.Se688Tyr mutation results in disruption of NMDA ligand binding and the p.Gly827Arg mutation results in disrupted gating of the ion channel. Our study highlights the importance of GRIN1 mutations in the etiology of isolated cases of early onset encephalopathy, and the valuable role of whole exome sequencing in identifying these mutations.

Keywords

De novo mutation; Early onset encephalopathy; GRIN1; Oculogyric movements.

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