我们报道了一名患有早期婴儿发作性癫痫的男性成年人,面部畸形,以及在PACS2中具有从头杂合突变的虹膜和脉络膜结肠瘤,即,c.625G>Ap.(Glu209Lys)。先前在患有PACS2相关疾病(早期婴儿癫痫性脑病66)的患者中报道了这种特定的突变。WDR37中的从头杂合突变已被证明会导致一种新的人类疾病,神经性心源性泌尿综合征(NOCGUS综合征)(OMIM#618652),以智力残疾为特征,面部畸形,和结肠瘤。根据大规模互动组数据,WDR37相互作用最强烈,到目前为止,PACS1和PACS2。临床上,结肠瘤已被描述为WDR37相关疾病和PACS1相关疾病(Schuurs-Hoeijmakers综合征)的特征,但不是与PACS2相关的疾病。我们对由WDR37,PACS1和PACS2突变引起的三种人类疾病的表型进行的审查显示癫痫的显着重叠,智力残疾,小脑萎缩,和面部特征。目前对这三种疾病的共同特征是结肠瘤的观察表明,这组基因可能与眼部发育有关。我们建议WDR37-PACS1-PACS2轴的失调导致一个可被智力残疾识别的频谱,独特的面部特征,和结肠瘤。
We report a male adult with early infantile-onset epilepsy, facial dysmorphism, and iridal and choroidal coloboma who had a de novo heterozygous mutation in PACS2, that is, c.625G > A p.(Glu209Lys). This specific mutation was previously reported in a patient with PACS2-related disorder (early infantile epileptic encephalopathy 66). De novo heterozygous mutations in
WDR37 have been shown to cause a novel human disorder, neurooculocardiogenitourinary syndrome (NOCGUS syndrome) (OMIM #618652), characterized by intellectual disability, facial dysmorphism, and coloboma. According to large-scale interactome data,
WDR37 interacts most strongly, by far, with PACS1 and PACS2. Clinically, coloboma has been described as a feature in a
WDR37-related disorder and a PACS1-related disorder (Schuurs-Hoeijmakers syndrome), but not in a PACS2-related disorder. Our review of the phenotypes of three human disorders caused by
WDR37, PACS1, and PACS2 mutations showed a significant overlap of epilepsy, intellectual disability, cerebellar atrophy, and facial features. The present observation of coloboma as a shared feature among these three disorders suggests that this group of genes may be involved in ocular development. We propose that dysregulation of the
WDR37-PACS1-PACS2 axis results in a spectrum that is recognizable by intellectual disability, distinctive facial features, and coloboma.