Infantile spasms is associated with deletion of the MAGI2 gene on chromosome 7q11.23-q21.11.
Infantile spasms (IS) is the most severe and common form of epilepsy occurring in the first year of life. At least half of IS cases are idiopathic in origin, with others presumed to arise because of brain insult or malformation. Here, we identify a locus for IS by high-resolution mapping of 7q11.23-q21.1 interstitial deletions in patients. The breakpoints delineate a 500 kb interval within the MAGI2 gene (1.4 Mb in size) that is hemizygously disrupted in 15 of 16 participants with IS or childhood epilepsy, but remains intact in 11 of 12 participants with no seizure history. MAGI2 encodes the synaptic scaffolding protein membrane-associated guanylate kinase inverted-2 that interacts with Stargazin, a protein also associated with epilepsy in the stargazer mouse.
Marshall
Christian R
CR
Program in Genetics & Genomic Biology and The Centre for Applied Genomics, Hospital for Sick Children, Toronto, ON M5G 1L7, Canada.
Young
Edwin J
EJ
Pani
Ariel M
AM
Freckmann
Mary-Louise
ML
Lacassie
Yves
Y
Howald
Cédric
C
Fitzgerald
Kristi K
KK
Peippo
Maarit
M
Morris
Colleen A
CA
Shane
Kate
K
Priolo
Manuela
M
Morimoto
Masafumi
M
Kondo
Ikuko
I
Manguoglu
Esra
E
Berker-Karauzum
Sibel
S
Edery
Patrick
P
Hobart
Holly H
HH
Mervis
Carolyn B
CB
Zuffardi
Orsetta
O
Reymond
Alexandre
A
Kaplan
Paige
P
Tassabehji
May
M
Gregg
Ronald G
RG
Scherer
Stephen W
SW
Osborne
Lucy R
LR
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D019457:Chromosome Breakage; D002886:Chromosomes, Human, Pair 17; D005260:Female; D017353:Gene Deletion; D005819:Genetic Markers; D051528:Guanylate Kinases; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008297:Male; D018895:Microsatellite Repeats; D020411:Oligonucleotide Array Sequence Analysis; D020161:Physical Chromosome Mapping; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D005819:Genetic Markers; D011506:Proteins; D051528:Guanylate Kinases; C485777:MAGI2 protein, human