title: Paternal germline mosaicism of a SCN2A mutation results in Ohtahara syndrome in half siblings.
abstract: Ohtahara syndrome is a devastating early infantile epileptic encephalopathy caused by mutations in different genes. We describe a patient with Ohtahara syndrome who presented on the first day of life with refractory tonic seizures and a suppression-burst pattern on EEG. The patient developed severe microcephaly, and never achieved any developmental milestones. He died at the age of 5 years. A de novo missense mutation (c. 4007C>A, p.S1336Y) in SCN2A was found. Interestingly, the father has another son with Ohtahara syndrome from a different mother. The half brother carries the same SCN2A mutation, strongly suggesting paternal gonadal mosaicism of the mutation. The broad clinical spectrum of SCN2A mutations now includes Ohtahara syndrome. This is the first report of familial Ohtahara syndrome due to a germline mosaic SCN2A mutation. Somatic mosaicism, including germline, has been described in several epileptic encephalopathies such as Dravet syndrome, KCNQ2 neonatal epileptic encephalopathy, SCN8A epileptic encephalopathy and STXBP1 related Ohtahara syndrome. Mosaicism should be considered as one of the important inheritance patterns when counseling parents with a child with these devastating diseases.
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Metabolic Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Zerem
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Metabolic Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel; Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Lev
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Metabolic Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Lubov
authors.initials: L
authors.lastname: Blumkin
authors.affiliation: Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Pediatrics and Adolescent Neurology, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel.
authors.forename: Hadassa
authors.initials: H
authors.lastname: Goldberg-Stern
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Metabolic Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Michaeli-Yossef
authors.affiliation: Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; Department of Pediatrics and Adolescent Neurology, Schneider Children's Medical Center of Israel, Petah Tiqwa, Israel.
authors.forename: Ayelet
authors.initials: A
authors.lastname: Halevy
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Metabolic Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Kivity
authors.affiliation: Department of Pediatrics, Yamagata University, Faculty of Medicine, Yamagata, Japan; Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Nakamura
authors.affiliation: Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Metabolic Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel; Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Esther
authors.initials: E
authors.lastname: Leshinsky-Silver
authors.affiliation: Department of Human Genetics, Yokohama City University, Graduate School of Medicine, Yokohama, Japan.
authors.forename: Hirotomo
authors.initials: H
authors.lastname: Saitsu
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel; Metabolic Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel; Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel; Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: asagie@post.tau.ac.il.
authors.forename: Tally
authors.initials: T
authors.lastname: Lerman-Sagie
mesh_terms: D058540:Aicardi Syndrome / Q000235:genetics*; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D005219:Father-Child Relations; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D008297:Male; D009030:Mosaicism; D009154:Mutation / Q000235:genetics*; D062551:NAV1.2 Voltage-Gated Sodium Channel / Q000235:genetics*; D035781:Siblings; D013036:Spasms, Infantile / Q000235:genetics*
chemical_list: D062551:NAV1.2 Voltage-Gated Sodium Channel; C568251:SCN2A protein, human
keywords: Channelopathies; Early infantile epileptic encephalopathy; Genetic counseling; Mosaic mutation; Suppression-burst