Abstract：
Niemann-Pick disease type C (NPC) is an autosomal recessive neurovisceral disease characterized by progressive neurodegeneration with variable involvement of multisystemic abnormalities. Crohn\'s disease (CD) is an inflammatory bowel disease (IBD) with a multifactorial etiology influenced by variants in NOD2. Here, we investigated a patient with plausible multisystemic overlapping manifestations of both NPC and CD. Her initial hospitalization was due to a prolonged fever and non-bloody diarrhea. A few months later, she presented with recurrent skin tags and anal fissures. Later, her neurological and pulmonary systems progressively deteriorated, leading to her death at the age of three and a half years. Differential diagnosis of her disease encompassed a battery of clinical testing and genetic investigations. The patient\'s clinical diagnosis was inconclusive. Specifically, the histopathological findings were directed towards an IBD disease. Nevertheless, the diagnosis of IBD was not consistent with the patient\'s subsequent neurological and pulmonary deterioration. Consequently, we utilized a genetic analysis approach to guide the diagnosis of this vague condition. Our phenotype-genotype association attempts led to the identification of candidate disease-causing variants in both NOD2 and NPC1. In this study, we propose a potential composite digenic impact of these two genes as the underlying molecular etiology. This work lays the foundation for future functional and mechanistic studies to unravel the digenic role of NOD2 and NPC1.
摘要：
尼曼-匹克病C型（NPC）是一种常染色体隐性遗传性神经内脏疾病，其特征是进行性神经变性，并涉及多系统异常。克罗恩病（CD）是一种炎症性肠病（IBD），其病因多因素受NOD2变异的影响。这里,我们调查了1例同时表现为NPC和CD的多系统重叠的患者.她最初的住院是由于长时间的发烧和非血性腹泻。几个月后,她出现了复发性皮肤标签和肛裂。稍后，她的神经和肺系统逐渐恶化，导致她在三岁半的时候去世。她的疾病的鉴别诊断包括一系列的临床测试和遗传研究。患者的临床诊断尚无定论。具体来说,组织病理学结果针对IBD疾病.然而，IBD的诊断与患者随后的神经和肺恶化不一致.因此,我们利用遗传分析方法来指导这种模糊病症的诊断。我们的表型-基因型关联尝试导致了NOD2和NPC1中候选致病变异的鉴定。在这项研究中,我们提出了这两个基因作为潜在分子病因的潜在复合双基因影响。这项工作为未来的功能和机理研究奠定了基础，以阐明NOD2和NPC1的双基因作用。
