Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance
Familial and sporadic 15q13.3 microdeletions in idiopathic generalized epilepsy: precedent for disorders with complex inheritance
复制标题
DOI：
10.1093/hmg/ddp311
复制
发表时间：
2009-10-01
影响因子：
3.5
通讯作者：
Berkovic, Samuel F.
中科院分区：
文献类型：
--
作者：
Dibbens, Leanne M.;Mullen, Saul;Berkovic, Samuel F.
在智力残疾、自闭症谱系障碍、精神分裂症和最近在特发性全身性癫痫（IGE）中已经描述了染色体位置15q13.3的微缺失。使用独立的IGE队列，我们首先旨在确认15q13.3缺失与IGE的关联。然后，我们着手确定散发性和家族性病例的相对发生率，并检查家族性病例中微缺失个体癫痫发作的可能性。15q13.3微缺失在7/539例（1.3%）不相关IGE病例中使用定量PCR或SNP阵列鉴定，并通过使用15q13.3区域特异性探针的阵列比较基因组杂交分析证实。使用家族研究追踪该病变的遗传。在先证者中发现的7个微缺失中，3个是新生的，2个是从未受影响的父母那里传播的，在2个病例中父母无法获得。4/7个家系未发现15q13.3缺失，3个家系中有其他IGE家系成员。比值比为68（95%置信区间29-181），表明致病性病变易患癫痫，具有复杂遗传和多重家族中表型IGE组分的不完全遗传。
Microdeletion at chromosomal position 15q13.3 has been described in intellectual disability, autism spectrum disorders, schizophrenia and recently in idiopathic generalized epilepsy (IGE). Using independent IGE cohorts, we first aimed to confirm the association of 15q13.3 deletions and IGE. We then set out to determine the relative occurrence of sporadic and familial cases and to examine the likelihood of having seizures for individuals with the microdeletion in familial cases. The 15q13.3 microdeletion was identified in 7 of 539 (1.3%) unrelated cases of IGE using quantitative PCR or SNP arrays and confirmed by array comparative genomic hybridization analysis using probes specific to the 15q13.3 region. The inheritance of this lesion was tracked using family studies. Of the seven microdeletions identified in probands, three were de novo, two were transmitted from an unaffected parent and in two cases the parents were unavailable. Non-penetrance of the microdeletion was identified in 4/7 pedigrees and three pedigrees included other family members with IGE who lacked the 15q13.3 deletion. The odds ratio is 68 (95% confidence interval 29-181), indicating a pathogenic lesion predisposing to epilepsy with complex inheritance and incomplete penetrance for the IGE component of the phenotype in multiplex families.