Missense mutations in the sodium-gated potassium channel gene KCNT1 cause severe autosomal dominant nocturnal frontal lobe epilepsy
Sarah E. Heron,Katherine R. Smith,Katherine R. Smith,Melanie Bahlo,Melanie Bahlo,Lino Nobili,Esther Kahana,Laura Licchetta,Karen Oliver,Aziz Mazarib,Zaid Afawi,Amos D. Korczyn,Giuseppe Plazzi,Steven Petrou,Steven Petrou,Samuel F. Berkovic,Ingrid E. Scheffer,Ingrid E. Scheffer,Ingrid E. Scheffer,Leanne M. Dibbens +19 more
TLDR
Findings implicate the sodium-gated potassium channel complex in ADNFLE and, more broadly, in the pathogenesis of focal epilepsies.Abstract:
We performed genomic mapping of a family with autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) and intellectual and psychiatric problems, identifying a disease-associated region on chromosome 9q34.3. Whole-exome sequencing identified a mutation in KCNT1, encoding a sodium-gated potassium channel subunit. KCNT1 mutations were identified in two additional families and a sporadic case with severe ADNFLE and psychiatric features. These findings implicate the sodium-gated potassium channel complex in ADNFLE and, more broadly, in the pathogenesis of focal epilepsies.read more
Citations
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Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders
Hane Lee,Joshua L. Deignan,Naghmeh Dorrani,Samuel P. Strom,Sibel Kantarci,Fabiola Quintero-Rivera,Kingshuk Das,Traci Toy,Bret Harry,Michael Yourshaw,Michelle Fox,Brent L. Fogel,Julian A. Martinez-Agosto,Derek Wong,Vivian Y. Chang,Perry B. Shieh,Christina G.S. Palmer,Katrina M. Dipple,Wayne W. Grody,Eric Vilain,Stanley F. Nelson +20 more
TL;DR: Initial clinical indications for CES referrals and molecular diagnostic rates for different indications and for different test types are reported, and trio-CES was associated with higher molecular diagnostic yield than proband-Ces or traditional molecular diagnostic methods.
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Targeted resequencing in epileptic encephalopathies identifies de novo mutations in CHD2 and SYNGAP1
Gemma L. Carvill,Sinéad Heavin,Simone C. Yendle,Jacinta M McMahon,Brian J. O'Roak,Joseph Cook,Adiba Khan,Michael O. Dorschner,Michael O. Dorschner,Molly Weaver,Molly Weaver,Sophie Calvert,Stephen M. Malone,Geoffrey Wallace,Thorsten Stanley,Ann M. E. Bye,Andrew Bleasel,Katherine B. Howell,Sara Kivity,Mark T Mackay,Victoria Rodriguez-Casero,Richard Webster,Amos D. Korczyn,Zaid Afawi,Nathanel Zelnick,Tally Lerman-Sagie,Tally Lerman-Sagie,Dorit Lev,Rikke S. Møller,Deepak Gill,Danielle M. Andrade,Jeremy L. Freeman,Lynette G. Sadleir,Jay Shendure,Samuel F. Berkovic,Ingrid E. Scheffer,Heather C Mefford +36 more
TL;DR: Target massively parallel resequencing of 19 known and 46 candidate genes for epileptic encephalopathy in 500 affected individuals (cases) to identify new genes involved and to investigate the phenotypic spectrum associated with mutations in known genes.
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The genetic landscape of the epileptic encephalopathies of infancy and childhood
Amy McTague,Amy McTague,Katherine B. Howell,Katherine B. Howell,J. Helen Cross,J. Helen Cross,Manju A. Kurian,Manju A. Kurian,Ingrid E. Scheffer +8 more
TL;DR: Gene discovery provides the basis for neurobiological insights, often showing convergence of mechanistic pathways that underpin the development of targeted therapies, which are essential to improve the outcome of these devastating disorders.
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Mutations in DEPDC5 cause familial focal epilepsy with variable foci
Leanne M. Dibbens,Boukje de Vries,Simona Donatello,Sarah E. Heron,Bree L. Hodgson,Satyan Chintawar,Douglas E. Crompton,James N. Hughes,Susannah T. Bellows,Karl Martin Klein,Karl Martin Klein,Petra M.C. Callenbach,Mark A. Corbett,Alison Gardner,Sara Kivity,Xenia Iona,Brigid M. Regan,Claudia M Weller,Denis Crimmins,Terence J. O'Brien,Rosa Guerrero-López,John C. Mulley,François Dubeau,Laura Licchetta,Francesca Bisulli,Patrick Cossette,Paul Q. Thomas,Jozef Gecz,José M. Serratosa,Oebele F. Brouwer,Frederick Andermann,Eva Andermann,Arn M. J. M. van den Maagdenberg,Massimo Pandolfo,Samuel F. Berkovic,Ingrid E. Scheffer,Ingrid E. Scheffer,Ingrid E. Scheffer +37 more
TL;DR: Study of families with focal epilepsy that were too small for conventional clinical diagnosis with FFEVF identified DEPDC5 mutations in approximately 12% of families, establishing high frequency mutations as a common cause of familial focal epilepsies.
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Epilepsy-associated genes.
Jie Wang,Zhi-Jian Lin,Zhi-Jian Lin,Liu Liu,Liu Liu,Haiqing Xu,Yi-Wu Shi,Yi-Wu Shi,Yong-Hong Yi,Yong-Hong Yi,Na He,Na He,Wei-Ping Liao,Wei-Ping Liao +13 more
TL;DR: This work found 977 genes that are associated with epilepsy and summarized the epilepsy-associated genes according to their function, with the goal of better characterize the association between genes and epilepsies and to further understand the mechanisms underlying epilepsy.
References
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Journal ArticleDOI
Autosomal dominant nocturnal frontal lobe epilepsy. A distinctive clinical disorder.
Ingrid E. Scheffer,Kailash P. Bhatia,Iscia Lopes-Cendes,David R. Fish,C D Marsden,Eva Andermann,F. Andermann,Richard Desbiens,D Keene,Fernando Cendes +9 more
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TL;DR: In this paper, a new locus for familial sleep-related focal epilepsy on chromosome 8p12.3-8q12.4 was identified, which is associated with mutations of the α4 and β2 subunits of the neuronal nicotinic acetylcholine receptor.
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