PRRT2 mutations: exploring the phenotypical boundaries
PRRT2 mutations: exploring the phenotypical boundaries
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DOI：
10.1136/jnnp-2013-305122
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发表时间：
2014-04-01
影响因子：
11
通讯作者：
Suls, Arvid
中科院分区：
文献类型：
--
作者：
Djemie, Tania;Weckhuysen, Sarah;Suls, Arvid
富脯氨酸跨膜蛋白2 （PRRT2）基因突变已在良性（家族性）婴儿惊厥（B(F)IC）、舞蹈病（ICCA）和阵发性运动障碍（pd）的婴儿惊厥患者中被发现。然而，PRRT2突变是否与其他癫痫综合征相关尚不清楚。我们在一个ICCA大家族中发现了PRRT2突变，该家族包含一个发热性癫痫发作（FS）个体和一个West综合征个体，我们分析了不同类型婴儿癫痫患者的异质队列中的PRRT2。方法筛选460例B(F)IC或ICCA、发热相关癫痫发作或婴儿癫痫性脑病患者。所有患者均采用直接测序法检测点突变。结果在16例病例中发现杂合突变，其中家族性病例10例，散发病例6例。所有患者均被诊断为B(F)IC、ICCA或PD。我们无法检测到任何其他癫痫综合征的突变。一些突变携带者在以后的生活中有学习障碍和/或精细运动技能受损。结论sprrt2突变似乎与FS或婴儿癫痫性脑病的病因无关。因此，B(F)IC、ICCA和PD仍然是与PRRT2突变相关的核心表型。在一些突变携带者中存在学习障碍或神经精神问题，需要更多的临床研究来更详细地解决这一发展方面的问题。
Background Mutations in the proline-rich transmembrane protein2 (PRRT2) gene have been identified in patients with benign (familial) infantile convulsions (B(F)IC), infantile convulsions with choreoathetosis (ICCA) and paroxysmal dyskinesias (PDs). However it remains unknown whether PRRT2 mutations are causal in other epilepsy syndromes. After we discovered a PRRT2 mutation in a large family with ICCA containing one individual with febrile seizures (FS) and one individual with West syndrome, we analysed PRRT2 in a heterogeneous cohort of patients with different types of infantile epilepsy.Methods We screened a cohort of 460 patients with B(F)IC or ICCA, fever related seizures or infantile epileptic encephalopathies. All patients were tested for point mutations using direct sequencing.Results We identified heterozygous mutations in 16 individuals: 10 familial and 6 sporadic cases. All patients were diagnosed with B(F)IC, ICCA or PD. We were not able to detect mutations in any of the other epilepsy syndromes. Several mutation carriers had learning disabilities and/or impaired fine motor skills later in life.ConclusionsPRRT2 mutations do not seem to be involved in the aetiology of FS or infantile epileptic encephalopathies. Therefore B(F)IC, ICCA and PD remain the core phenotypes associated with PRRT2 mutations. The presence of learning disabilities or neuropsychiatric problems in several mutation carriers calls for additional clinical studies addressing this developmental aspect in more detail.