Gene Panel Testing in Epileptic Encephalopathies and Familial Epilepsies

被引：101

作者：

Moller, Rikke S. ^{[1
,2
]}

Larsen, Line H. G. ^{[3
]}

Johannesen, Katrine M. ^{[1
,2
]}

Talvik, Inga ^{[12
,13
]}

Talvik, Tiina ^{[13
,14
]}

Vaher, Ulvi ^{[13
,14
]}

Miranda, Maria J. ^{[4
]}

Farooq, Muhammad ^{[11
,15
]}

Nielsen, Jens E. K. ^{[5
]}

Svendsen, Lene Lavard ^{[6
]}

Kjelgaard, Ditte B. ^{[1
]}

Linnet, Karen M. ^{[7
]}

Hao, Qin ^{[3
]}

Uldall, Peter ^{[1
]}

Frangu, Mimoza ^{[9
]}

Tommerup, Niels ^{[11
]}

Baig, Shahid M. ^{[15
]}

Abdullah, Uzma ^{[11
,15
]}

Born, Alfred P. ^{[10
]}

Gellert, Pia ^{[1
]}

Nikanorova, Marina ^{[1
,2
]}

Olofsson, Kern ^{[1
]}

Jepsen, Birgit ^{[1
]}

Marjanovic, Dragan ^{[1
]}

Al-Zehhawi, Lana I. K. ^{[8
]}

Penalva, Sofia J. ^{[16
]}

Krag-Olsen, Bente ^{[7
]}

Brusgaard, Klaus ^{[3
]}

Hjalgrim, Helle ^{[1
,2
]}

Rubboli, Guido ^{[1
]}

Pal, Deb K. ^{[17
]}

Dahl, Hans A. ^{[3
]}

机构：

[1] Filadelfia, Danish Epilepsy Ctr, Dianalund, Denmark

[2] Univ Southern Denmark, Inst Reg Hlth Serv, Odense, Denmark

[3] Amplexa Genet, Odense, Denmark

[4] Univ Copenhagen, Herlev Univ Hosp, Pediat Neurol, Dept Pediat, Herlev, Denmark

[5] Roskilde Hosp, Sect Gynaecol Obstet & Paediat, Dept Clin Med, Roskilde, Denmark

[6] Hvidovre Univ Hosp, Dept Pediat, Hvidovre, Denmark

[7] Aarhus Univ Hosp, Dept Pediat, Aarhus, Denmark

[8] Aarhus Univ Hosp, Dept Clin Genet, Aarhus, Denmark

[9] Holbaek Cent Hosp, Dept Pediat, Holbaek, Denmark

[10] Copenhagen Univ Hosp, Rigshosp, Dept Paediat, Copenhagen, Denmark

[11] Univ Copenhagen, Wilhelm Johannsen Ctr Funct Genome Res, Dept Cellular & Mol Med, Copenhagen, Denmark

[12] Tallinn Childrens Hosp, Tallinn, Estonia

[13] Tartu Univ Hosp, Childrens Clin, Tartu, Estonia

[14] Univ Tartu, Dept Paediat, Tartu, Estonia

[15] Natl Inst Biotechnol & Genet Engn NIBGE PIEAS, Human Mol Genet Lab, Hlth Biotechnol Div, Faisalabad, Pakistan

[16] CEMIC, Dept Genet, Buenos Aires, DF, Argentina

[17] Kings Coll London, Inst Psychiat Psychol & Neurosci, Dept Basic & Clin Neurosci, London, England

来源：

MOLECULAR SYNDROMOLOGY | 2016年 / 7卷 / 04期

关键词：

Epileptic encephalopathies; Familial epilepsies; Gene panel testing; Seizures;

D O I：

10.1159/000448369

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

In recent years, several genes have been causally associated with epilepsy. However, making a genetic diagnosis in a patient can still be difficult, since extensive phenotypic and genetic heterogeneity has been observed in many monogenic epilepsies. This study aimed to analyze the genetic basis of a wide spectrum of epilepsies with age of onset spanning from the neonatal period to adulthood. A gene panel targeting 46 epilepsy genes was used on a cohort of 216 patients consecutively referred for panel testing. The patients had a range of different epilepsies from benign neonatal seizures to epileptic encephalopathies (EEs). Potentially causative variants were evaluated by literature and database searches, submitted to bioinformatic prediction algorithms, and validated by Sanger sequencing. If possible, parents were included for segregation analysis. We identified a presumed disease-causing variant in 49 (23%) of the 216 patients. The variants were found in 19 different genes including SCN1A, STXBP1, CDKL5, SCN2A, SCN8A, GABRA1, KCNA2, and STX1B. Patients with neonatal-onset epilepsies had the highest rate of positive findings (57%). The overall yield for patients with EEs was 32%, compared to 17% among patients with generalized epilepsies and 16% in patients with focal or multifocal epilepsies. By the use of a gene panel consisting of 46 epilepsy genes, we were able to find a disease-causing genetic variation in 23% of the analyzed patients. The highest yield was found among patients with neonatal-onset epilepsies and EEs. (C) 2016 S. Karger AG, Basel

引用

页码：210 / 219

页数：10

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