A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA)

TY - JOUR

T1 - A balanced translocation disrupts SYNGAP1 in a patient with intellectual disability, speech impairment, and epilepsy with myoclonic absences (EMA)

AU - Klitten, Laura L

AU - Møller, Rikke S

AU - Nikanorova, Marina

AU - Silahtaroglu, Asli

AU - Hjalgrim, Helle

AU - Tommerup, Niels

N1 - Wiley Periodicals, Inc. © 2011 International League Against Epilepsy.

PY - 2011/12

Y1 - 2011/12

N2 - 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.

AB - 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.

KW - Adult

KW - Chromosomes, Human, Pair 22

KW - Chromosomes, Human, Pair 6

KW - Cytogenetics

KW - Epilepsies, Myoclonic

KW - Humans

KW - Intellectual Disability

KW - Male

KW - Methacrylates

KW - Mutation

KW - Speech Disorders

KW - Translocation, Genetic

KW - ras GTPase-Activating Proteins

U2 - 10.1111/j.1528-1167.2011.03304.x

DO - 10.1111/j.1528-1167.2011.03304.x

M3 - Journal article

C2 - 22050443

SN - 0780-0150

VL - 52

SP - e190-3

JO - Epilepsia-lehti

JF - Epilepsia-lehti

IS - 12

ER -