Dazzo Emanuela, Santulli Lia, Posar Annio, Fattouch Jinane, Conti Sara, Lodén-van Straaten Martin, Mijalkovic Jona, De Bortoli Marzia, Rosa Maurizio, Millino Caterina, Pacchioni Beniamina, Di Bonaventura Carlo, Giallonardo Anna Teresa, Striano Salvatore, Striano Pasquale, Parmeggiani Antonia, Nobile Carlo
CNR-Neuroscience Institute, Section of Padua, Padova, Italy.
Department of Neurological Sciences, Federico II University, Napoli, Italy.
Epilepsy Res. 2015 Feb;110:132-8. doi: 10.1016/j.eplepsyres.2014.12.004. Epub 2014 Dec 16.
Autosomal dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy syndrome characterized by prominent auditory or aphasic symptoms. Mutations in LGI1 account for less than 50% of ADLTE families. We assessed the impact of LGI1 microrearrangements in a collection of ADLTE families and sporadic lateral temporal epilepsy (LTE) patients, and investigated novel ADLTE and LTE patients.
Twenty-four ADLTE families and 140 sporadic LTE patients with no evidence of point mutations in LGI1 were screened for copy number alterations using multiplex ligation-dependent probe amplification (MLPA). Newly ascertained familial and sporadic LTE patients were clinically investigated, and interictal EEG and MRI findings were obtained; probands were tested for LGI1 mutations by direct exon sequencing or denaturing high performance liquid chromatography.
We identified a novel microdeletion spanning LGI1 exon 2 in a family with two affected members, both presenting focal seizures with visual symptoms. Also, we identified a novel LGI1 missense mutation (c.1118T > C; p.L373S) in a newly ascertained family with focal seizures with prominent visual auras, and another missense mutation (c.856T > C; p.C286R) in a sporadic patient with auditory seizures.
We describe two novel ADLTE families with predominant visual auras segregating pathogenic LGI1 mutations. These findings support the notion that, in addition to auditory symptoms, other types of auras can be found in patients carrying LGI1 mutations. The identification of a novel microdeletion in LGI1, the second so far identified, suggests that LGI1 microrearrangements may not be exceptional.
常染色体显性遗传性外侧颞叶癫痫（ADLTE）是一种遗传性局灶性癫痫综合征，以突出的听觉或失语症状为特征。LGI1基因的突变在ADLTE家族中所占比例不到50%。我们评估了LGI1基因微重排在一组ADLTE家族和散发性外侧颞叶癫痫（LTE）患者中的影响，并对新的ADLTE和LTE患者进行了研究。
对24个ADLTE家族和140例无LGI1基因点突变证据的散发性LTE患者，采用多重连接依赖探针扩增技术（MLPA）筛查拷贝数改变。对新确诊的家族性和散发性LTE患者进行临床研究，获取发作间期脑电图和磁共振成像结果；通过直接外显子测序或变性高效液相色谱法检测先证者的LGI1基因突变。
我们在一个有两名受累成员的家族中发现了一个新的跨越LGI1基因外显子2的微缺失，两名患者均表现为伴有视觉症状的局灶性发作。此外，我们在一个新确诊的有突出视觉先兆的局灶性发作家族中发现了一个新的LGI1错义突变（c.1118T>C；p.L373S），在一名有听觉发作的散发性患者中发现了另一个错义突变（c.856T>C；p.C286R）。
我们描述了两个以主要视觉先兆为特征的新的ADLTE家族，其致病的LGI1基因突变呈分离状态。这些发现支持了这样一种观点，即除听觉症状外，携带LGI1基因突变的患者还可出现其他类型的先兆。LGI1基因中一个新的微缺失的发现，这是迄今为止发现的第二个，表明LGI1基因微重排可能并非罕见。
