进行性脑病,水肿,心律失常,和视神经萎缩(PEHO)综合征是一种不寻常的孟德尔表型,其起源不明,导致严重的智力残疾,视神经/小脑萎缩,癫痫发作,发展进步,踏板水肿,和早逝。无特征受影响的个体通常被归类为患有PEHO样综合征,尽管他们可能被误诊为癫痫性脑病,早产的潜在结果。在这项研究中,我们报道了一个血缘关系的沙特家族,其CCDC88A基因的新纯合无义突变导致PEHO样综合征。孩子们患有发育迟缓,癫痫,精神残疾,视神经/小脑萎缩,和踏板水肿。对患有该疾病的家庭成员进行全外显子组测序以研究新突变。全外显子组测序数据分析,通过随后的Sanger测序验证确认,鉴定出一个新的纯合无义突变c。1292G>A,这是由p.Trp431*停止增益引起的。在100个无关的健康对照中排除了这种突变。在该研究中检测到的无义纯合突变在文献或各种数据库中尚未被报道为致病性的。总之,CCDC88A第12外显子的突变导致蛋白质功能完全丧失。这种损失可能导致PEHO表型。因此,CCDC88A基因可能在正常人神经发育的多个方面发挥重要和关键的作用。
Progressive encephalopathy, edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an unusual Mendelian phenotype of unidentified origin that causes profound intellectual disability, optic nerve/cerebellar atrophy, epileptic seizures, developmental progress, pedal edema, and early death. Uncharacteristic affected individuals are often classified as having PEHO-like syndrome, although they may be misdiagnosed as having epileptic encephalopathy, a potential result of early birth. In this study, we report a consanguineous Saudi family with a novel homozygous nonsense mutation of the CCDC88A gene causing PEHO-like syndrome. The children were suffering from developmental delay, epilepsy, mental disability, optic nerve/cerebellar atrophy, and pedal edema. Whole exome sequencing was conducted for the members of the family who have the disorder to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation, identified a novel homozygous nonsense mutation c. 1292G > A, which was caused by p.Trp431* stop gain. This mutation was ruled out in 100 unrelated healthy controls. The nonsense homozygous mutation detected in this study has not yet been reported as pathogenic in the literature or various databases. In conclusion, a complete loss of protein function due to premature stop gain was caused by a mutation in exon 12 of CCDC88A. This loss may lead to PEHO phenotype. CCDC88A gene may therefore play an important and critical role for multiple aspects of normal human neurodevelopment.