Protocadherin 19 mutations in girls with infantile-onset epilepsy
Protocadherin 19 mutations in girls with infantile-onset epilepsy
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DOI：
10.1212/wnl.0b013e3181ed9e67
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发表时间：
2010-08-17
期刊：
影响因子：
9.9
通讯作者：
Guerrini, R.
中科院分区：
文献类型：
--
作者：
Marini, C.;Mei, D.;Guerrini, R.
目的：为探讨PCDH 19基因（Xq 22）在女性癫痫发病中的作用，对117例女性热性惊厥（FS）患者进行PCDH 19基因突变筛查，发现13例先证者（11%）存在PCDH 19基因点突变。癫痫发作时的平均年龄为8.5个月; 8例患者（62%）表现为FS，4例（33%）表现为局灶性癫痫发作簇，1例表现为新发癫痫持续状态（SE）。随后的癫痫发作类型包括无热强直阵挛性、发热性和无热SE、失神、肌阵挛性和局灶性癫痫发作。7例患者（54%）的临床诊断与Dravet综合征（DS）一致; 6例（46%）患有局灶性癫痫。在大多数患者中，癫痫发作在发作时特别频繁，呈簇状出现，并随着年龄的增长而变得不那么频繁。11例患者存在精神发育迟滞，范围从轻度（7; 64%）到中度（1; 9%）到重度（3; 27%）。5例患者（38%）有与精神发育迟滞相关的自闭症特征。突变为错义突变（6）、截短突变（2）、移码突变（3）和剪接突变（2）。11个是新的突变。突变遗传在3个先证者（25%）：2个明显未受影响的父亲和1个从母亲谁曾全面epileps.Conclusions：PCDH 19是新兴的一个主要基因为家族性或散发性癫痫发作的女性患者或不精神发育迟滞。在我们的队列中，具有DS样特征的癫痫性脑病和不同严重程度的局灶性癫痫是相关的表型，并且具有相同的代表性。神经病学（R）2010; 75：646-653
Objective: To explore the causative role of PCDH19 gene (Xq22) in female patients with epilepsy.Methods: We studied a cohort of 117 female patients with febrile seizures (FS) and a wide spectrum of epilepsy phenotypes including focal and generalized forms with either sporadic or familial distribution.Results: PCDH19 screening showed point mutations in 13 probands (11%). Mean age at seizure onset was 8.5 months; 8 patients (62%) presented with FS, 4 (33%) with cluster of focal seizures, and 1 with de novo status epilepticus (SE). Subsequent seizure types included afebrile tonic-clonic, febrile, and afebrile SE, absences, myoclonic, and focal seizures. Seven patients (54%) had a clinical diagnosis consistent with Dravet syndrome (DS); 6 (46%) had focal epilepsy. In most patients, seizures were particularly frequent at onset, manifesting in clusters and becoming less frequent with age. Mental retardation was present in 11 patients, ranging from mild (7; 64%) to moderate (1; 9%) to severe (3; 27%). Five patients (38%) had autistic features in association to mental retardation. Mutations were missense (6), truncating (2), frameshift (3), and splicing (2). Eleven were new mutations. Mutations were inherited in 3 probands (25%): 2 from apparently unaffected fathers and 1 from a mother who had had generalized epilepsy.Conclusions: PCDH19 is emerging as a major gene for infantile-onset familial or sporadic epilepsy in female patients with or without mental retardation. In our cohort, epileptic encephalopathy with DS-like features and focal epilepsy of variable severity were the associated phenotypes and were equally represented. Neurology (R) 2010; 75: 646-653