Cardiac Investigations in Sudden Unexpected Death in DEPDC5-Related Epilepsy.
Cardiac Investigations in Sudden Unexpected Death in DEPDC5-Related Epilepsy.
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DEPDC5相关癫痫患者意外猝死的心脏检查
DOI：
10.1002/ana.26256
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发表时间：
2022-01
影响因子：
11.2
通讯作者：
Baulac, Stephanie
中科院分区：
文献类型：
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作者：
Bacq, Alexandre;Roussel, Delphine;Bonduelle, Thomas;Zagaglia, Sara;Maletic, Marina;Ribierre, Theo;Adle-Biassette, Homa;Marchal, Cecile;Jennesson, Melanie;An, Isabelle;Picard, Fabienne;Navarro, Vincent;Sisodiya, Sanjay M.;Baulac, Stephanie
DEPDC 5及其哺乳动物雷帕霉素靶蛋白（mTOR）阻遏物GATOR 1复合物的结合伴侣（NPRL 2/3）中的种系功能丧失突变可导致局灶性癫痫并增加癫痫猝死（SUDEP）的风险。在这里，我们询问DEPDC 5单倍不足是否易患原发性心脏缺陷，这些缺陷可能导致SUDEP，从而影响SUDEP高风险患者的临床管理。在16例DEPDC 5、NPRL 2或NPRL 3致病性变异患者中进行了临床心脏检查。产生了两种新的Depdc 5小鼠品系，一种人HA标记的Depdc 5品系和一种具有第二等位基因（Depdc 5 c/−）的神经元特异性缺失的Depdc 5杂合敲除，以研究Depdc 5在癫痫发作期间SUDEP和心脏活动中的作用。霍尔特、超声心动图和心电图（ECG）检查未提供患者队列中临床心功能改变的证据，其中3例DEPDC 5患者死于SUDEP，6例有SUDEP家族史。在尸检DEPDC 5 SUDEP病例中，尸检时没有心脏损伤。HA标记的Depdc 5小鼠显示Depdc 5在脑、心脏和肺中表达。对Depdc 5 c/−小鼠的同步脑电图-ECG记录显示，导致SUDEP样事件的自发性癫痫发作之前没有心律失常。小鼠和人类数据显示，在DEPDC 5相关癫痫谱中，结构性或功能性心脏损伤均不可能是SUDEP的主要原因。神经网络2022;91：101-116
Germline loss‐of‐function mutations in DEPDC5, and in its binding partners (NPRL2/3) of the mammalian target of rapamycin (mTOR) repressor GATOR1 complex, cause focal epilepsies and increase the risk of sudden unexpected death in epilepsy (SUDEP). Here, we asked whether DEPDC5 haploinsufficiency predisposes to primary cardiac defects that could contribute to SUDEP and therefore impact the clinical management of patients at high risk of SUDEP. Clinical cardiac investigations were performed in 16 patients with pathogenic variants in DEPDC5, NPRL2, or NPRL3. Two novel Depdc5 mouse strains, a human HA‐tagged Depdc5 strain and a Depdc5 heterozygous knockout with a neuron‐specific deletion of the second allele (Depdc5 c/−), were generated to investigate the role of Depdc5 in SUDEP and cardiac activity during seizures. Holter, echocardiographic, and electrocardiographic (ECG) examinations provided no evidence for altered clinical cardiac function in the patient cohort, of whom 3 DEPDC5 patients succumbed to SUDEP and 6 had a family history of SUDEP. There was no cardiac injury at autopsy in a postmortem DEPDC5 SUDEP case. The HA‐tagged Depdc5 mouse revealed expression of Depdc5 in the brain, heart, and lungs. Simultaneous electroencephalographic–ECG records on Depdc5 c/− mice showed that spontaneous epileptic seizures resulting in a SUDEP‐like event are not preceded by cardiac arrhythmia. Mouse and human data show neither structural nor functional cardiac damage that might underlie a primary contribution to SUDEP in the spectrum of DEPDC5‐related epilepsies. ANN NEUROL 2022;91:101–116
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DOI：
10.1038/s41436-018-0060-2
发表时间：
2019-03
期刊：
Genetics in medicine : official journal of the American College of Medical Genetics
影响因子：
--
作者：
Baldassari S;Picard F;Verbeek NE;van Kempen M;Brilstra EH;Lesca G;Conti V;Guerrini R;Bisulli F;Licchetta L;Pippucci T;Tinuper P;Hirsch E;de Saint Martin A;Chelly J;Rudolf G;Chipaux M;Ferrand-Sorbets S;Dorfmüller G;Sisodiya S;Balestrini S;Schoeler N;Hernandez-Hernandez L;Krithika S;Oegema R;Hagebeuk E;Gunning B;Deckers C;Berghuis B;Wegner I;Niks E;Jansen FE;Braun K;de Jong D;Rubboli G;Talvik I;Sander V;Uldall P;Jacquemont ML;Nava C;Leguern E;Julia S;Gambardella A;d'Orsi G;Crichiutti G;Faivre L;Darmency V;Benova B;Krsek P;Biraben A;Lebre AS;Jennesson M;Sattar S;Marchal C;Nordli DR Jr;Lindstrom K;Striano P;Lomax LB;Kiss C;Bartolomei F;Lepine AF;Schoonjans AS;Stouffs K;Jansen A;Panagiotakaki E;Ricard-Mousnier B;Thevenon J;de Bellescize J;Catenoix H;Dorn T;Zenker M;Müller-Schlüter K;Brandt C;Krey I;Polster T;Wolff M;Balci M;Rostasy K;Achaz G;Zacher P;Becher T;Cloppenborg T;Yuskaitis CJ;Weckhuysen S;Poduri A;Lemke JR;Møller RS;Baulac S
通讯作者：
Baulac S
影响因子：
6.1
作者：
De Fusco, Antonio;Cerullo, Maria Sabina;Benfenati, Fabio
通讯作者：
Benfenati, Fabio
影响因子：
5.7
作者：
Bardai, Abdennasser;Blom, Marieke T.;Tan, Hanno L.
通讯作者：
Tan, Hanno L.
影响因子：
12.7
作者：
Baldassari, Sara;Ribierre, Theo;Baulac, Stephanie
通讯作者：
Baulac, Stephanie
影响因子：
9.9
作者：
Balestrini S;Mikati MA;Álvarez-García-Rovés R;Carboni M;Hunanyan AS;Kherallah B;McLean M;Prange L;De Grandis E;Gagliardi A;Pisciotta L;Stagnaro M;Veneselli E;Campistol J;Fons C;Pias-Peleteiro L;Brashear A;Miller C;Samões R;Brankovic V;Padiath QS;Potic A;Pilch J;Vezyroglou A;Bye AME;Davis AM;Ryan MM;Semsarian C;Hollingsworth G;Scheffer IE;Granata T;Nardocci N;Ragona F;Arzimanoglou A;Panagiotakaki E;Carrilho I;Zucca C;Novy J;Dzieżyc K;Parowicz M;Mazurkiewicz-Bełdzińska M;Weckhuysen S;Pons R;Groppa S;Sinden DS;Pitt GS;Tinker A;Ashworth M;Michalak Z;Thom M;Cross JH;Vavassori R;Kaski JP;Sisodiya SM
通讯作者：
Sisodiya SM