Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders
Clinical and genetic aspects of PCDH19-related epilepsy syndromes and the possible role of PCDH19 mutations in males with autism spectrum disorders
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DOI：
10.1007/s10048-013-0353-1
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发表时间：
2013-02-01
期刊：
影响因子：
2.2
通讯作者：
Brilstra, E. H.
中科院分区：
文献类型：
--
作者：
van Harssel, J. J. T.;Weckhuysen, S.;Brilstra, E. H.
由PCDH19突变引起的女性癫痫和智力低下（EFMR）具有可变的临床表现，需要进一步探索。癫痫发作可能由发热引起，类似Dravet综合征。此外，传播男性没有癫痫发作，但据报道有僵硬的个性，暗示可能的自闭症谱系障碍（ASD）。因此，本研究旨在确定Dravet样和EFMR女性患者和ASD男性患者中与PCDH 19突变相关的表型谱。我们筛选了120名患有Dravet样癫痫的女性，136名具有EFMR特征的女性和20名患有ASD的男性。将PCDH 19突变携带者的表型和基因型与文献报道的125例女性EFMR进行比较。我们报告了另外15例PCDH19突变患者。对所有报告患者的临床数据进行审查，结果显示EFMR的临床表现具有异质性，但婴儿期癫痫发作、发热敏感性和癫痫发作的发生是关键特征。大多数病人在青少年时期癫痫发作得到缓解。智力残疾和行为障碍很常见。50%的突变是错义突变，仅位于细胞外结构域。截短突变已在所有蛋白质结构域中鉴定。一个ASD先证者携带一个错义突变，预测有有害的影响，这表明在男性ASD可以与PCDH19突变。
Epilepsy and mental retardation limited to females (EFMR), caused by PCDH19 mutations, has a variable clinical expression that needs further exploration. Onset of epilepsy may be provoked by fever and can resemble Dravet syndrome. Furthermore, transmitting males have no seizures, but are reported to have rigid personalities suggesting possible autism spectrum disorders (ASD). Therefore, this study aimed to determine the phenotypic spectrum associated with PCDH19 mutations in Dravet-like and EFMR female patients and in males with ASD. We screened 120 females suffering from Dravet-like epilepsy, 136 females with EFMR features and 20 males with ASD. Phenotypes and genotypes of the PCDH19 mutation carriers were compared with those of 125 females with EFMR reported in the literature. We report 15 additional patients with a PCDH19 mutation. Review of clinical data of all reported patients showed that the clinical picture of EFMR is heterogeneous, but epilepsy onset in infancy, fever sensitivity and occurrence of seizures in clusters are key features. Seizures remit in the majority of patients during teenage years. Intellectual disability and behavioural disturbances are common. Fifty percent of all mutations are missense mutations, located in the extracellular domains only. Truncating mutations have been identified in all protein domains. One ASD proband carried one missense mutation predicted to have a deleterious effect, suggesting that ASD in males can be associated with PCDH19 mutations.