Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia
Autosomal dominant epilepsy with auditory features: a new LGI1 family including a phenocopy with cortical dysplasia
复制标题
DOI：
10.1007/s00415-015-7921-2
复制
发表时间：
2016-01-01
影响因子：
6
通讯作者：
Helbig, Ingo
中科院分区：
文献类型：
--
作者：
Klein, Karl Martin;Pendziwiat, Manuela;Helbig, Ingo
我们报告一个新的常染色体显性遗传性癫痫伴听觉特征(ADEAF)家系，包括先证者的局灶性皮质发育不良(FCD)。我们的目标是确定该家族的分子病因，并阐明FCD与ADEAF的关系。包括14名癫痫发作患者在内的一个伊朗犹太大家庭的表型包括高分辨率3-T磁共振成像。我们进行了连锁分析和外显子组测序。对LGI1、KANK1和RELN进行Sanger测序。11例患者的癫痫症状与ADEAF一致。先证者接受了右侧近侧颞叶FCD的手术。4个个体的3-T磁共振成像结果并不明显。连锁分析在染色体9p24(LOD 2.43)和10q22-25(LOD 2.04)上出现峰。除先证者表现出表型外，在所有患者中都发现了一种新的杂合子LGI1突变。外显子组测序没有发现染色体9p24区域内的变异。KANK1中紧密定位的变异体和RELN变异体不与表型分离。我们提供了一个新的LGI1突变的大型ADEAF家族的表型谱的详细描述，该突变在FCD先证者中明显缺失，表明尽管临床症状相同，ADEAF家族中可能存在表型突变。这个家系表明，一个家族中罕见的癫痫综合征既可以有遗传原因，也有结构原因。
We report a new family with autosomal dominant epilepsy with auditory features (ADEAF) including focal cortical dysplasia (FCD) in the proband. We aim to identify the molecular cause in this family and clarify the relationship between FCD and ADEAF. A large Iranian Jewish family including 14 individuals with epileptic seizures was phenotyped including high-resolution 3-T MRI. We performed linkage analysis and exome sequencing. LGI1, KANK1 and RELN were Sanger sequenced. Seizure semiology of 11 individuals was consistent with ADEAF. The proband underwent surgery for right mesiotemporal FCD. 3-T MRIs in four individuals were unremarkable. Linkage analysis revealed peaks on chromosome 9p24 (LOD 2.43) and 10q22-25 (LOD 2.04). A novel heterozygous LGI1 mutation was identified in all affected individuals except for the proband indicating a phenocopy. Exome sequencing did not reveal variants within the chromosome 9p24 region. Closely located variants in KANK1 and a RELN variant did not segregate with the phenotype. We provide detailed description of the phenotypic spectrum within a large ADEAF family with a novel LGI1 mutation that was conspicuously absent in the proband with FCD, demonstrating that despite identical clinical symptoms, phenocopies in ADEAF families may exist. This family illustrates that rare epilepsy syndromes within a single family can have both genetic and structural etiologies.