title: A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA).
abstract: Epilepsy with myoclonic absences (EMA) is a rare form of generalized epilepsy occurring in childhood and is often difficult to treat. The underlying etiology of EMA is unknown in the majority of patients. Herein, we describe a patient with EMA and intellectual disability who carries a de novo balanced translocation: t(6;22)(p21.32;q11.21). We mapped the translocation breakpoints by fluorescence in situ hybridization (FISH), and the breakpoint at 6p21.32 was found to truncate the N-methyl-d-aspartate (NMDA)-receptor associated gene SYNGAP1. The breakpoint at 22q11.21 was within a highly variable region without known protein-coding genes. Mutations of SYNGAP1 are associated with nonsyndromal intellectual disability (NSID). Two-thirds of the patients described so far also have generalized epilepsy. This finding, together with our report, suggests that dysfunction of SYNGAP1 contributes to the development of generalized epilepsy, including EMA.
authors: Danish Epilepsy Center, Dianalund, Denmark. klitten@sund.ku.dk
authors: Laura L
authors: LL
authors: Klitten
authors: Rikke S
authors: RS
authors: Møller
authors: Marina
authors: M
authors: Nikanorova
authors: Asli
authors: A
authors: Silahtaroglu
authors: Helle
authors: H
authors: Hjalgrim
authors: Niels
authors: N
authors: Tommerup
mesh_terms: D000328:Adult; D002892:Chromosomes, Human, Pair 22; D002896:Chromosomes, Human, Pair 6; D003582:Cytogenetics; D004831:Epilepsies, Myoclonic / Q000150:complications / Q000235:genetics*; D006801:Humans; D008607:Intellectual Disability / Q000150:complications / Q000235:genetics*; D008297:Male; D008689:Methacrylates; D009154:Mutation; D013064:Speech Disorders / Q000150:complications / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*; D020703:ras GTPase-Activating Proteins / Q000235:genetics*
chemical_list: C498353:G-Bond; D008689:Methacrylates; C484739:SYNGAP1 protein, human; D020703:ras GTPase-Activating Proteins