Epileptic spasms are a feature of DEPDC5 mTORopathy.
Epileptic spasms are a feature of DEPDC5 mTORopathy.
复制标题
DOI：
10.1212/nxg.0000000000000016
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Mefford HC
中科院分区：
文献类型：
--
作者：
Carvill GL;Crompton DE;Regan BM;McMahon JM;Saykally J;Zemel M;Schneider AL;Dibbens L;Howell KB;Mandelstam S;Leventer RJ;Harvey AS;Mullen SA;Berkovic SF;Sullivan J;Scheffer IE;Mefford HC
评估癫痫痉挛患者队列中DEPDC 5突变的存在。我们对130例痉挛患者进行了DEPDC 5重测序，对感兴趣的变异进行了分离分析，并对可能和可能致病的变异患者进行了详细的临床评估。我们在130例痉挛患者队列中确定了3例DEPDC 5变异患者。我们还描述了另外3例DEPDC 5改变和癫痫痉挛的患者：2例来自先前描述的家族，第三例通过临床试验确定。总体而言，我们描述了来自5个家族的6例痉挛和DEPDC 5变异体患者; 2例新发，3例为家族性。两个人有局灶性皮质发育不良。临床结局高度可变。虽然最近在癫痫痉挛的分子研究结果强调了从头突变的贡献，我们强调了遗传突变的相关性，在设置的家族史的局灶性癫痫。我们还说明了实用的临床诊断测试和详细的表型评价在表征星座的表型与DEPDC 5改变。我们将这一表型谱扩展到包括癫痫痉挛，使DEPDC 5癫痫与其他mTORopathies的公认特征更加一致。
To assess the presence of DEPDC5 mutations in a cohort of patients with epileptic spasms. We performed DEPDC5 resequencing in 130 patients with spasms, segregation analysis of variants of interest, and detailed clinical assessment of patients with possibly and likely pathogenic variants. We identified 3 patients with variants in DEPDC5 in the cohort of 130 patients with spasms. We also describe 3 additional patients with DEPDC5 alterations and epileptic spasms: 2 from a previously described family and a third ascertained by clinical testing. Overall, we describe 6 patients from 5 families with spasms and DEPDC5 variants; 2 arose de novo and 3 were familial. Two individuals had focal cortical dysplasia. Clinical outcome was highly variable. While recent molecular findings in epileptic spasms emphasize the contribution of de novo mutations, we highlight the relevance of inherited mutations in the setting of a family history of focal epilepsies. We also illustrate the utility of clinical diagnostic testing and detailed phenotypic evaluation in characterizing the constellation of phenotypes associated with DEPDC5 alterations. We expand this phenotypic spectrum to include epileptic spasms, aligning DEPDC5 epilepsies more with the recognized features of other mTORopathies.