Hsu Tina, Coughlin Carrie C, Monaghan Kristin G, Fiala Elise, McKinstry Robert C, Paciorkowski Alex R, Shinawi Marwan
Washington University School of Medicine, St Louis, MO, USA.
Division of Dermatology, Department of Medicine, Washington University School of Medicine, St Louis, MO, USA.
Child Neurol Open. 2017 Oct 8;4:2329048X17733214. doi: 10.1177/2329048X17733214. eCollection 2017 Jan-Dec.
Synaptosomal-associated protein 29 (SNAP29) is a t-SNARE protein that is implicated in intracellular vesicle fusion. Mutations in the gene have been associated with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome (CEDNIK). In patients with 22q11.2 deletion syndrome, mutations in on the nondeleted chromosome are linked to similar ichthyotic and neurological phenotypes. Here, the authors report a patient with cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome who presented with global developmental delay, polymicrogyria, dysgenesis of the corpus callosum, optic nerve dysplasia, gaze apraxia, and dysmorphic features. He has developed ichthyosis and palmoplantar keratoderma as he has grown. Exome sequencing identified a homozygous nonsense mutation in gene designated as c.85C>T (p.Arg29X). The authors compare the findings in the proband with previously reported cases. The previously unreported mutation in this patient and his phenotype add to the characterization of cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome and the accumulating scientific evidence that implicates synaptic protein dysfunction in various neuroectodermal conditions.
突触体相关蛋白29（SNAP29）是一种参与细胞内囊泡融合的t-SNARE蛋白。该基因的突变与脑发育不全、神经病变、鱼鳞病和角皮病综合征（CEDNIK）有关。在22q11.2缺失综合征患者中，未缺失染色体上该基因的突变与类似的鱼鳞病和神经学表型相关。在此，作者报告了一名患有脑发育不全、神经病变、鱼鳞病和角皮病综合征的患者，该患者表现为全面发育迟缓、多小脑回、胼胝体发育不全、视神经发育异常、凝视失用和畸形特征。随着年龄增长，他出现了鱼鳞病和掌跖角化病。外显子组测序在该基因中鉴定出一个纯合无义突变，命名为c.85C>T（p.Arg29X）。作者将先证者的研究结果与先前报道的病例进行了比较。该患者先前未报道的突变及其表型，进一步丰富了脑发育不全、神经病变、鱼鳞病和角皮病综合征的特征，也为越来越多的科学证据提供了补充，这些证据表明突触蛋白功能障碍与各种神经外胚层疾病有关。
