Michelucci Roberto, Poza Juan Jose, Sofia Vito, de Feo Maria Rita, Binelli Simona, Bisulli Francesca, Scudellaro Evan, Simionati Barbara, Zimbello Rosanna, D'Orsi Giuseppe, Passarelli Daniela, Avoni Patrizia, Avanzini Giuliano, Tinuper Paolo, Biondi Roberto, Valle Giorgio, Mautner Victor F, Stephani Ulrich, Tassinari Carlo Alberto, Moschonas Nicholas K, Siebert Reiner, Lopez de Munain Adolpho, Perez-Tur Jordi, Nobile Carlo
Dipartimento di Neuroscienze, Divisione di Neurologia, Ospedale Bellaria e Università di Bologna, Bologna, Italy.
Epilepsia. 2003 Oct;44(10):1289-97. doi: 10.1046/j.1528-1157.2003.20003.x.
[corrected] To describe the clinical and genetic findings of seven additional pedigrees with autosomal dominant lateral temporal epilepsy (ADLTE).
A personal and family history was obtained from each affected and unaffected member, along with a physical and neurologic examination. Routine and sleep EEGs, computed tomography (CT), or magnetic resonance imaging (MRI) were performed in almost all the patients. DNAs from family members were typed with several microsatellite markers localized on either side of LGI1 at 10q24 and screened for LGI1 mutations.
The seven families included a total of 34 affected individuals (10 deceased). The age at onset ranged between 8 and 50 years (average, 22 years). Twenty-six patients had clear-cut focal (elementary, complex, or secondarily generalized) seizures, characterized by prominent auditory auras in 68% of the cases. Less frequent ictal symptoms were visual, psychic, or aphasic seizures, the latter occurring in isolation in one family. The attacks were rare and well controlled by antiepileptic drug treatment but recurred after drug discontinuation. Interictal EEGs were usually unrevealing. MRI or CT scans were negative. Analysis of LGI1/Epitempin exons failed to show mutations in three pedigrees. Linkage analysis strongly suggested exclusion of linkage in one of these families. We found two novel missense mutations, a T-->C substitution in exon 6 at position 598, and a T-->A transition in exon 8 at position 1295, the latter being detected in a family with aphasic seizures.
Our data confirm the inclusion of aphasic seizures within the ADLTE clinical spectrum, suggest the existence of locus heterogeneity in ADLTE, and provide new familial cases with LGI1 missense mutations associated with the disease.
[修正后]描述另外7个常染色体显性遗传性外侧颞叶癫痫（ADLTE）家系的临床及遗传学特征。
收集每位受累及未受累家庭成员的个人史及家族史，并进行体格检查和神经系统检查。几乎所有患者均进行了常规及睡眠脑电图、计算机断层扫描（CT）或磁共振成像（MRI）检查。使用位于10q24的LGI1两侧的多个微卫星标记对家庭成员的DNA进行分型，并筛查LGI1突变。
这7个家系共有34名受累个体（10名已故）。发病年龄在8至50岁之间（平均22岁）。26例患者有明确的局灶性（基本型、复杂型或继发性全身性）发作，68%的病例以明显的听觉先兆为特征。发作期症状较少见的有视觉、精神性或失语性发作，后者在一个家系中单独出现。发作很少见，抗癫痫药物治疗可很好地控制，但停药后会复发。发作间期脑电图通常无异常发现。MRI或CT扫描均为阴性。对LGI1/Epitempin外显子的分析未能在3个家系中发现突变。连锁分析强烈提示其中1个家系不存在连锁关系。我们发现了2个新的错义突变，外显子6第598位的T→C替换以及外显子8第1295位的T→A转换，后者在一个有失语性发作的家系中被检测到。
我们的数据证实失语性发作属于ADLTE临床谱，提示ADLTE存在基因座异质性，并提供了与该疾病相关的携带LGI1错义突变的新家族病例。
