A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity.
A systematic review and meta-analysis of 271 PCDH19-variant individuals identifies psychiatric comorbidities, and association of seizure onset and disease severity.
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DOI：
10.1038/s41380-018-0066-9
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发表时间：
2019-03
影响因子：
11
通讯作者：
Gecz J
中科院分区：
文献类型：
--
作者：
Kolc KL;Sadleir LG;Scheffer IE;Ivancevic A;Roberts R;Pham DH;Gecz J
女性癫痫和智力低下 (EFMR) 是一种婴儿期发病的疾病，其特征是丛集性癫痫发作。 EFMR 是由 X 染色体基因 PCDH19 突变引起的，并且由于女性 X 染色体失活或男性体细胞突变而导致细胞嵌合体。这篇综述描述了这种疾病的神经精神病学特征，并研究了临床和分子因素与神经精神病学结果的关联。数据提取自 38 篇经过同行评审的原始文章，其中包括 271 个个案。我们发现，与发病 > 12 个月相比，癫痫发作 ≤ 12 个月与更严重的智力障碍显着相关 (p = 4.127 × 10−7)。我们确定了两个复发变体 p.Asn340Ser 和 p.Tyr366Leufs*10，分别出现在 25 例（20 例不相关）和 30 例（11 例不相关）病例中。 PCDH19 突变与约 60% 的女性、80% 受影响的嵌合男性的精神合并症相关，并在 9 名半合子男性中报告。最常报告的是多动症、自闭症和强迫症特征。在具有复发性变异的个体或整个群体中不存在基因型-表型关联。癫痫发作年龄可用于提供更多信息的预后咨询。
Epilepsy and Mental Retardation Limited to Females (EFMR) is an infantile onset disorder characterized by clusters of seizures. EFMR is due to mutations in the X-chromosome gene PCDH19, and is underpinned by cellular mosaicism due to X-chromosome inactivation in females or somatic mutation in males. This review characterizes the neuropsychiatric profile of this disorder and examines the association of clinical and molecular factors with neuropsychiatric outcomes. Data were extracted from 38 peer-reviewed original articles including 271 individual cases. We found that seizure onset ≤12 months was significantly associated (p = 4.127 × 10−7) with more severe intellectual disability, compared with onset >12 months. We identified two recurrent variants p.Asn340Ser and p.Tyr366Leufs*10 occurring in 25 (20 unrelated) and 30 (11 unrelated) cases, respectively. PCDH19 mutations were associated with psychiatric comorbidities in approximately 60% of females, 80% of affected mosaic males, and reported in nine hemizygous males. Hyperactive, autistic, and obsessive-compulsive features were most frequently reported. There were no genotype–phenotype associations in the individuals with recurrent variants or the group overall. Age at seizure onset can be used to provide more informative prognostic counseling.
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影响因子：
2.2
作者：
de Lange IM;Rump P;Neuteboom RF;Augustijn PB;Hodges K;Kistemaker AI;Brouwer OF;Mancini GMS;Newman HA;Vos YJ;Helbig KL;Peeters-Scholte C;Kriek M;Knoers NV;Lindhout D;Koeleman BPC;van Kempen MJA;Brilstra EH
通讯作者：
Brilstra EH
影响因子：
56.9
作者：
CHUGANI, HT;PHELPS, ME
通讯作者：
PHELPS, ME
影响因子：
3.9
作者：
Depienne, Christel;Trouillard, Oriane;Bouteiller, Delphine;Gourfinkel-An, Isabelle;Poirier, Karine;Rivier, Francois;Berquin, Patrick;Nabbout, Rima;Chaigne, Denys;Steschenko, Dominique;Gautier, Agnes;Hoffman-Zacharska, Dorota;Lannuzel, Annie;Lackmy-Port-Lis, Marilyn;Maurey, Helene;Dusser, Anne;Bru, Marie;Gilbert-Dussardier, Brigitte;Roubertie, Agathe;Kaminska, Anna;Whalen, Sandra;Mignot, Cyril;Baulac, Stephanie;Lesca, Gaetan;Arzimanoglou, Alexis;LeGuern, Eric
通讯作者：
LeGuern, Eric
影响因子：
9.9
作者：
Cetica, Valentina;Chiari, Sara;Guerrini, Renzo
通讯作者：
Guerrini, Renzo
影响因子：
4.5
作者：
Depienne, Christel;Bouteiller, Delphine;Keren, Boris;Cheuret, Emmanuel;Poirier, Karine;Trouillard, Oriane;Benyahia, Baya;Quelin, Chloe;Carpentier, Wassila;Julia, Sophie;Afenjar, Alexandra;Gautier, Agnes;Rivier, Francois;Meyer, Sophie;Berquin, Patrick;Helias, Marie;Py, Isabelle;Rivera, Serge;Bahi-Buisson, Nadia;Gourfinkel-An, Isabelle;Cazeneuve, Cecile;Ruberg, Merle;Brice, Alexis;Nabbout, Rima;LeGuern, Eric
通讯作者：
LeGuern, Eric