Novel De Novo PCDH19 Mutations in Three Unrelated Females With Epilepsy Female Restricted Mental Retardation Syndrome
Novel De Novo PCDH19 Mutations in Three Unrelated Females With Epilepsy Female Restricted Mental Retardation Syndrome
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DOI：
10.1002/ajmg.a.33611
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发表时间：
2010-10-01
影响因子：
2
通讯作者：
Milunsky, Jeff M.
中科院分区：
文献类型：
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作者：
Jamal, Seema M.;Basran, Raveen K.;Milunsky, Jeff M.
1971年[Juberg and Hellman，1971]首次描述了15例早发性癫痫大发作和精神发育迟滞的相关女性癫痫和精神发育迟滞（EFMR）[OMIM 300088]。虽然EFMR表现为X连锁遗传，但它遵循一种不寻常的模式，即不影响传播男性，只影响杂合子女性。在2008年，原钙粘蛋白19（PCDH 19）基因内的突变被认为是EFMR的病因[Dibbens等人（2008）; Nat Genet 40：776-781]。EFMR表型的典型特征是婴儿期癫痫发作和轻度至重度智力障碍。一些患有EFMR的人也被描述为具有自闭症特征。我们描述了三个无关的女性个体，年龄从3岁到19岁不等，与从头新的PCDH 19突变。这三个人都在婴儿期癫痫发作，需要使用多种抗癫痫药物。他们也有不同程度的智力障碍，沿着自闭症特征的出现。尽管迄今为止描述的大多数EFMR患者都表现出这种不寻常的家族性X连锁遗传，但我们的三名具有新发突变的无关女性突出了在早发性癫痫、智力障碍和自闭症特征的女性中检测PCDH 19的重要性，无论其家族史如何。(C)2010 Wiley-Liss，Inc.
Epilepsy and Mental Retardation limited to Females (EFMR) [OMIM 300088] was first described in 1971 [Juberg and Hellman, 1971] in 15 related females with early onset grand mal seizures and mental retardation. Although EFMR demonstrates X-linked inheritance, it follows an unusual pattern by sparing transmitting males and affecting only heterozygous females. In 2008, mutations within the protocadherin 19 (PCDH19) gene were implicated as causative of EFMR [Dibbens et al. (2008); Nat Genet 40:776-781]. The EFMR phenotype is typically characterized by seizure onset in infancy and mild to severe intellectual impairment. Several individuals with EFMR have also been described as having autistic features. We describe three unrelated female individuals, ranging in age from 3 to 19 years, with de novo novel PCDH19 mutations. All three individuals have seizure onset in infancy and require the use of multiple antiepileptic drugs. They also have varying degrees of intellectual impairment along with the presence of autistic features. Although most individuals with EFMR described to date demonstrate this unusual familial X-linked inheritance, our three unrelated females with de novo mutations highlight the importance of testing PCDH19 in females with early onset epilepsy, intellectual impairment, and autistic features, regardless of family history. (C) 2010 Wiley-Liss, Inc.