Novel PRRT2 mutations in paroxysmal dyskinesia patients with variant inheritance and phenotypes
Novel PRRT2 mutations in paroxysmal dyskinesia patients with variant inheritance and phenotypes
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具有变异遗传和表型的阵发性运动障碍患者中的新 PRRT2 突变
DOI：
10.1111/gbb.12008
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发表时间：
2013-03-01
影响因子：
2.5
通讯作者：
Liao, W-P
中科院分区：
文献类型：
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作者：
Liu, X-R;Wu, M.;Liao, W-P
阵发性运动障碍是一组发作性运动障碍，在临床表现上具有显著的可变性，并与癫痫有潜在的联系。PRRT2已被确定为pd的致病基因，但PRRT2突变的表型和遗传模式有待进一步阐明。在这项研究中，收集了10例家族性和21例散发性pd和pd相关表型的病例。通过直接测序筛选基因组DNA中的PRRT2突变。在9例（90.0%）家族性病例和6例（28.6%）散发性病例中鉴定出7个PRRT2突变。5个突变是新发现的：2个错义突变(c.647C . >G/p。Pro216Arg和c.872C>T/p。Ala291Val)和三个截断突变(c.117delA/p。Val41TyrfsX49 c.510dupT / p。Leu171SerfsX3和c.579dupA/p.Glu194ArgfsX6)。家族性病例多为常染色体显性遗传，外显率不完全。在散发性病例中，遗传是异质性的，包括隐性遗传与复合杂合突变，遗传突变与不完全亲本外显率和新生突变。在36.0%的受影响病例中发现与PRRT2突变相关的变异表型，包括热惊厥、癫痫、婴儿非惊厥发作（INCS）和夜间惊厥（NC）。所有未报道的INCS或NC患者在脑电图（EEG）上均表现异常。典型的婴儿惊厥和阵发性舞蹈病(ICCA)/阵发性运动障碍（PKD）患者无脑电图异常记录。我们的研究进一步证实，PRRT2突变是家族性pd最常见的原因，表现为显性和隐性遗传。伴有PRRT2突变的ICCA/PKD患者可能偶尔发生癫痫。不同表型INCS或NC不同于经典ICCA/PKD的临床和脑电图。它们与癫痫有一些相似之处，但不完全相同，可能代表ICCA/PKD与癫痫之间的重叠。
Paroxysmal dyskinesias (PDs) are a group of episodic movement disorders with marked variability in clinical manifestation and potential association with epilepsy. PRRT2 has been identified as a causative gene for PDs, but the phenotypes and inheritance patterns of PRRT2 mutations need further clarification. In this study, 10 familial and 21 sporadic cases with PDs and PDs‐related phenotypes were collected. Genomic DNA was screened for PRRT2 mutations by direct sequencing. Seven PRRT2 mutations were identified in nine (90.0%) familial cases and in six (28.6%) sporadic cases. Five mutations are novel: two missense mutations (c.647C>G/p.Pro216Arg and c.872C>T/p.Ala291Val) and three truncating mutations (c.117delA/p.Val41TyrfsX49, c.510dupT/p.Leu171SerfsX3 and c.579dupA/p.Glu194ArgfsX6). Autosomal dominant inheritance with incomplete penetrance was observed in most of the familial cases. In the sporadic cases, inheritance was heterogeneous including recessive inheritance with compound heterozygous mutations, inherited mutations with incomplete parental penetrance and de novo mutation. Variant phenotypes associated with PRRT2 mutations, found in 36.0% of the affected cases, included febrile convulsions, epilepsy, infantile non‐convulsive seizures (INCS) and nocturnal convulsions (NC). All patients with INCS or NC, not reported previously, displayed abnormalities on electroencephalogram (EEG). No EEG abnormalities were recorded in patients with classical infantile convulsions and paroxysmal choreoathetosis (ICCA)/paroxysmal kinesigenic dyskinesia (PKD). Our study further confirms that PRRT2 mutations are the most common cause of familial PDs, displaying both dominant and recessive inheritance. Epilepsy may occasionally occur in ICCA/PKD patients with PRRT2 mutations. Variant phenotypes INCS or NC differ from classical ICCA/PKD clinically and electroencephalographically. They have some similarities with, but not identical to epilepsy, possibly represent an overlap between ICCA/PKD and epilepsy.