Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences
Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences
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DOI：
10.1111/epi.12009
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发表时间：
2012-12-01
期刊：
影响因子：
5.6
通讯作者：
Gambardella, Antonio
中科院分区：
文献类型：
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作者：
Labate, Angelo;Tarantino, Patrizia;Gambardella, Antonio
编码富含脯氨酸的跨膜蛋白2的PRRT2杂合突变与包括良性家族性婴儿癫痫(BFIs)或家族性阵发性运动性肌张力障碍(PKD)在内的不同表型相关。我们报告一个有BFIS/PKD表型的近亲意大利家庭，有14名在世成员和6名患病个体(4名男性，年龄从644岁不等)。我们鉴定了已报道的PRRT2基因c.649dupC(p.Arg217ProsX8)突变，该突变与疾病共分离，在100名匹配祖先的对照中未观察到。4例BFIS表型患者为该突变杂合子，包括BFIS/PKD表型较严重的两个患病兄弟的近亲父母，发作性共济失调和缺失，他们是唯一携带纯合子c.649dupC突变的个体。这个家系提供了强有力的证据表明，PRRT2纯合子突变会导致更严重的临床疾病，如智力低下、发作性共济失调和失神，从而扩大了与PRRT2突变相关的临床谱系。此外，它表明了双倍剂量的基因突变的相加效应，并强调了该基因突变的表型后果的复杂性。
Heterozygous mutations of PRRT2, which encodes proline-rich transmembrane protein 2, are associated with heterogeneous phenotypes including benign familial infantile seizures (BFIS), or familial paroxysmal kinesigenic dystonia (PKD). We report a consanguineous Italian family with BFIS/PKD phenotype that contained 14 living members with 6 affected individuals (four men, ranging in age from 644 years). We identified the reported c.649dupC (p.Arg217ProfsX8) mutation of PRRT2 gene that cosegregated with the disease and was not observed in 100 controls of matched ancestry. Four patients with BFIS phenotype were heterozygous for this mutation, including the consanguineous parents of the two affected brothers with more severe phenotypes of BFIS/PKDmental retardation, episodic ataxia, and absenceswho were the only individuals to carry a homozygous c.649dupC mutation. This family provides strong evidence that homozygous PRRT2 mutations give rise to more severe clinical disease of mental retardation, episodic ataxia, and absences, and, thus, enlarges the clinical spectrum related to PRRT2 mutations. Moreover, it suggests an additive effect of double dose of the genetic mutation and underscores the complexity of the phenotypic consequences of mutations in this gene.