Genetic analysis of PRRT2 for benign infantile epilepsy, infantile convulsions with choreoathetosis syndrome, and benign convulsions with mild gastroenteritis.
OBJECTIVE
PRRT2 mutations were recently identified in benign familial infantile epilepsy (BFIE) and infantile convulsions with paroxysmal choreoathetosis (ICCA) but no abnormalities have so far been identified in their phenotypically similar seizure disorder of benign convulsions with mild gastroenteritis (CwG), while mutations in KCNQ2 and KCNQ3 have been recognized in benign familial neonatal epilepsy (BFNE). The aim of this study was to identify PRRT2 mutations in infantile convulsions in Asian families with BFIE and ICCA, CwG and BFNE.


METHODS
We recruited 26 unrelated Japanese affected with either BFIE or non-familial benign infantile seizures and their families, including three families with ICCA. A total of 17 Japanese and Taiwanese with CwG, 50 Japanese with BFNE and 96 healthy volunteers were also recruited. Mutations of PRRT2 were sought using direct sequencing.


RESULTS
Heterozygous truncation mutation (c.649dupC) was identified in 15 of 26 individuals with benign infantile epilepsy (52.1%). All three families of ICCA harbored the same mutation (100%). Another novel mutation (c.1012+2dupT) was found in the proband of a family with BFIE. However, no PRRT2 mutation was found in either CwG or BFNE.


CONCLUSIONS
The results confirm that c.649dupC, a truncating mutation of PRRT2, is a hotspot mutation resulting in BFIE or ICCA regardless of the ethnic background. In contrast, PRRT2 mutations do not seem to be associated with CwG or BFNE. Screening for PRRT2 mutation might be useful in early-stage differentiation of BFIE from CwG.
Department of Pediatrics, School of Medicine, Fukuoka University, Fukuoka, Japan.
Atsushi
A
Ishii
Sawa
S
Yasumoto
Yukiko
Y
Ihara
Takahito
T
Inoue
Takako
T
Fujita
Noriko
N
Nakamura
Masaharu
M
Ohfu
Yushiro
Y
Yamashita
Hideo
H
Takatsuka
Toshiaki
T
Taga
Rie
R
Miyata
Masahiro
M
Ito
Hiroshi
H
Tsuchiya
Taro
T
Matsuoka
Tetsuya
T
Kitao
Kiyotaka
K
Murakami
Wang-Tso
WT
Lee
Sunao
S
Kaneko
Shinichi
S
Hirose
D000293:Adolescent; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D002819:Chorea / Q000235:genetics*; D020936:Epilepsy, Benign Neonatal / Q000150:complications / Q000235:genetics*; D005192:Family Health; D005260:Female; D005759:Gastroenteritis / Q000150:complications / Q000235:genetics*; D005820:Genetic Testing; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human