Chromosome loci vary by juvenile myoclonic epilepsy subsyndromes: linkage and haplotype analysis applied to epilepsy and EEG 3.5-6.0 Hz polyspike waves.
Chromosome loci vary by juvenile myoclonic epilepsy subsyndromes: linkage and haplotype analysis applied to epilepsy and EEG 3.5-6.0 Hz polyspike waves.
复制标题
DOI：
10.1002/mgg3.195
复制
发表时间：
2016-03
影响因子：
2
通讯作者：
Delgado-Escueta AV
中科院分区：
文献类型：
--
作者：
Wight JE;Nguyen VH;Medina MT;Patterson C;Durón RM;Molina Y;Lin YC;Martínez-Juárez IE;Ochoa A;Jara-Prado A;Tanaka M;Bai D;Aftab S;Bailey JN;Delgado-Escueta AV
青少年肌阵挛性癫痫（JME），最常见的遗传性癫痫，仍然是一个谜，因为它被认为是一种疾病，而不是几种疾病。我们确定了来自洪都拉斯的三个大型多代/多重JME家系，具有不同的JME亚综合征，包括儿童失神癫痫演变为JME（CAE/JME;家系1），JME与青少年发作的精神分裂症缺失（JME/PA;家系2）和经典JME（cJME;家系3）。所有表型均得到验证，包括各种癫痫的有症状者、EEG 3.5-6.0 Hz多棘波的无症状者和EEG正常的无症状者。使用基于癫痫/EEG诊断的四种诊断模型，对单个家系和合并家系的5185个单核苷酸多态性进行两点参数连锁分析。还对每个个体进行了整个基因组的单倍型分析。在家系1中，单倍型确定了一个34 cM的区域在2q21.2-q31.1共分离与所有受影响的成员，一个区域接近2q14.3确定的连锁（Z最大值= 1.77;家系1）。在家系2中，连锁和单倍型鉴定了13q13.3-q31.2的44 cM共分离区域（13q31.1处Z max = 3.50;合并家系）。在家系3中，单倍型鉴定在17 q12的6cM共分离区域。在家系3的13q14.2和1 q32中也发现了可能的共分离，但由于关键个体中存在无信息标记，因此无法明确证实。在特定的JME亚综合征中鉴定的不同染色体区域可能包含单独的JME致病基因，这有利于JME作为几种不同疾病的概念。全外显子组测序可能会在2q21.2-2q31.1中识别CAE/JME基因，在13q13.3-q31.2中识别JME/pA基因，在17 q12中识别cJME基因。
Juvenile myoclonic epilepsy (JME), the most common genetic epilepsy, remains enigmatic because it is considered one disease instead of several diseases. We ascertained three large multigenerational/multiplex JME pedigrees from Honduras with differing JME subsyndromes, including Childhood Absence Epilepsy evolving to JME (CAE/JME; pedigree 1), JME with adolescent onset pyknoleptic absence (JME/pA; pedigree 2), and classic JME (cJME; pedigree 3). All phenotypes were validated, including symptomatic persons with various epilepsies, asymptomatic persons with EEG 3.5–6.0 Hz polyspike waves, and asymptomatic persons with normal EEGs. Two‐point parametric linkage analyses were performed with 5185 single‐nucleotide polymorphisms on individual pedigrees and pooled pedigrees using four diagnostic models based on epilepsy/EEG diagnoses. Haplotype analyses of the entire genome were also performed for each individual. In pedigree 1, haplotyping identified a 34 cM region in 2q21.2–q31.1 cosegregating with all affected members, an area close to 2q14.3 identified by linkage (Z max = 1.77; pedigree 1). In pedigree 2, linkage and haplotyping identified a 44 cM cosegregating region in 13q13.3–q31.2 (Z max = 3.50 at 13q31.1; pooled pedigrees). In pedigree 3, haplotyping identified a 6 cM cosegregating region in 17q12. Possible cosegregation was also identified in 13q14.2 and 1q32 in pedigree 3, although this could not be definitively confirmed due to the presence of uninformative markers in key individuals. Differing chromosome regions identified in specific JME subsyndromes may contain separate JME disease‐causing genes, favoring the concept of JME as several distinct diseases. Whole‐exome sequencing will likely identify a CAE/JME gene in 2q21.2–2q31.1, a JME/pA gene in 13q13.3–q31.2, and a cJME gene in 17q12.