Klein Karl Martin, Pendziwiat Manuela, Cohen Rony, Appenzeller Silke, de Kovel Carolien G F, Rosenow Felix, Koeleman Bobby P C, Kuhlenbäumer Gregor, Sheintuch Liron, Veksler Ronel, Friedman Alon, Afawi Zaid, Helbig Ingo
Department of Neurology, Epilepsy Center Frankfurt Rhine-Main, Center of Neurology and Neurosurgery, University Hospital, Goethe-University Frankfurt, Frankfurt, Germany.
Department of Neurology, Epilepsy Center Hessen, University Hospitals Giessen and Marburg, Philipps-University Marburg, Marburg, Germany.
J Neurol. 2016 Jan;263(1):11-6. doi: 10.1007/s00415-015-7921-2. Epub 2015 Oct 12.
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.
我们报告了一个新的常染色体显性遗传性听觉特征癫痫（ADEAF）家系，先证者存在局灶性皮质发育不良（FCD）。我们旨在确定该家系的分子病因，并阐明FCD与ADEAF之间的关系。对一个包括14名癫痫发作个体的大型伊朗犹太人家系进行了表型分析，包括高分辨率3-T磁共振成像（MRI）。我们进行了连锁分析和外显子组测序。对LGI1、KANK1和RELN进行了桑格测序。11名个体的癫痫发作症状与ADEAF一致。先证者接受了右侧颞叶内侧FCD手术。4名个体的3-T MRI检查无异常。连锁分析在9号染色体p24区域（LOD 2.43）和10号染色体q22-25区域（LOD 2.04）发现了峰值。除先证者外，在所有受影响个体中均发现了一种新的杂合LGI1突变，提示存在表型模拟。外显子组测序未在9号染色体p24区域发现变异。KANK1中位置相近的变异和一个RELN变异与表型不连锁。我们详细描述了一个大型ADEAF家系的表型谱，该家系存在一种新的LGI1突变，在先证者的FCD中明显不存在，这表明尽管临床症状相同，但ADEAF家系中可能存在表型模拟。这个家系表明，单个家系中的罕见癫痫综合征可能具有遗传和结构病因。
