PDF(Pubmed)
Abstract：
Developmental and epileptic encephalopathy-9 (DEE9) is characterized by seizure onset in infancy, mild to severe intellectual impairment, and psychiatric features and is caused by a mutation in the PCDH19 gene on chromosome Xq22. The rare, unusual X-linked type of disorder affects heterozygous females and mosaic males; transmitting males are unaffected. In our study, 165 patients with epilepsy were tested by Next Generation Sequencing (NGS)-based panel and exome sequencing using Illumina technology. PCDH19 screening identified three point mutations, one indel, and one 29 bp-long deletion in five unrelated female probands. Two novel mutations, c.1152_1180del (p.Gln385Serfs*6) and c.830_831delinsAA (p.Phe277*), were identified and found to be de novo pathogenic. Moreover, among the three inherited mutations, two originated from asymptomatic mothers and one from an affected father. The PCDH19 c.1682C>T and c.1711G>T mutations were present in the DNA samples of asymptomatic mothers. After targeted parental testing, X chromosome inactivation tests and Sanger sequencing were carried out for mosaicism examination on maternal saliva samples in the two asymptomatic PCDH19 mutation carrier subjects. Tissue mosaicism and X-inactivation tests were negative. Our results support the opportunity for reduced penetrance in DEE9 and contribute to expanding the genotype-phenotype spectrum of PCDH19-related epilepsy.
摘要：
发育性和癫痫性脑病-9（DEE9）的特征是婴儿期癫痫发作，轻度至重度智力障碍，和精神病学特征，是由Xq22染色体上的PCDH19基因突变引起的。罕见的，不寻常的X连锁型疾病会影响杂合雌性和马赛克雄性；传播雄性不受影响。在我们的研究中,使用Illumina技术，通过基于下一代测序（NGS）的小组和外显子组测序对165例癫痫患者进行了测试。PCDH19筛查确定了三个点突变，一个indel,五个无关的女性先证者中有一个29bp长的缺失。两个新的突变,c.1152_1180del（p。Gln385Serfs*6）和c.830_831delinsAA（p。Phe277*),被鉴定并发现是从头致病的。此外，在三个遗传突变中，两个来自无症状的母亲，一个来自受影响的父亲。PCDH19c.1682C>T和c.1711G>T突变存在于无症状母亲的DNA样本中。在有针对性的家长测试之后，对两名无症状PCDH19突变携带者的母体唾液样本进行了X染色体失活测试和Sanger测序，以进行镶嵌性检查。组织镶嵌和X失活试验均为阴性。我们的结果支持DEE9外显率降低的机会，并有助于扩大PCDH19相关癫痫的基因型-表型谱。
