Febrile infection-related epilepsy syndrome (FIRES) is not caused by SCN1A, POLG, PCDH19 mutations or rare copy number variations.
OBJECTIVE
Febrile infection-related epilepsy syndrome (FIRES) is an enigmatic seizure disorder in childhood with an innocuous febrile infection triggering severe and intractable multifocal epilepsy, mostly with status epilepticus. FIRES shares several phenotypic features with epilepsies seen in patients with protocadherin 19 (PCDH19), sodium channel protein type 1 subunit alpha (SCN1A), and DNA polymerase subunit gamma-1 (POLG) mutations. The aim of the study was the mutation analysis of these prime candidate genes in a cohort of patients with FIRES. Additionally, given that rare copy number variations (CNVs) have recently been established as important risk factors for epilepsies, we performed a genome-wide CNV analysis.


METHODS
We analysed the protein coding region, including splice sites of the three candidate genes in 15 patients (eight males, seven females) with FIRES (age at onset 3-15 y, median 6) using Sanger sequencing. Inclusion criteria were a status epilepticus without identifiable cause and a preceding febrile infection in previously healthy children. In addition, we performed genome-wide human single-nucleotide polymorphism 6.0 arrays in a subset of 10 patients to identify pathological CNVs.


RESULTS
We could not identify the most likely pathogenic mutations or CNVs in FIRES.


CONCLUSIONS
Mutations in PCDH19, SCN1A, POLG, or CNVs are not responsible for FIRES.
Institute of Experimental Medicine, Christian-Albrechts-University, Kiel, Germany. s.appenzeller@neurologie.uni-kiel.de
Silke
S
Appenzeller
Ingo
I
Helbig
Ulrich
U
Stephani
Martin
M
Häusler
Gerhard
G
Kluger
May
M
Bungeroth
Stefanie
S
Müller
Gregor
G
Kuhlenbäumer
Andreas
A
van Baalen
D000293:Adolescent; D015820:Cadherins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations / Q000235:genetics; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D006801:Humans; D007239:Infections / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D011247:Pregnancy; D000091363:Protocadherins; D003294:Seizures, Febrile / Q000235:genetics*; D013577:Syndrome
D015820:Cadherins; D062550:NAV1.1 Voltage-Gated Sodium Channel; C438605:PCDH19 protein, human; D000091363:Protocadherins; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human