{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T01:12:50Z","timestamp":1792804370012,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T00:00:00Z","timestamp":1653782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Research of Jordan University of Science and Technology","award":["83\/2018"],"award-info":[{"award-number":["83\/2018"]}],"id":[{"id":"https:\/\/ror.org\/03y8mtb59","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Niemann\u2013Pick disease type C (NPC) is an autosomal recessive neurovisceral disease characterized by progressive neurodegeneration with variable involvement of multisystemic abnormalities. Crohn\u2019s 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\u2019s 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\u2019s subsequent neurological and pulmonary deterioration. Consequently, we utilized a genetic analysis approach to guide the diagnosis of this vague condition. Our phenotype\u2013genotype 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.<\/jats:p>","DOI":"10.3390\/genes13060973","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:50:51Z","timestamp":1653814251000},"page":"973","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Potential Composite Digenic Contribution of NPC1 and NOD2 Leading to Atypical Lethal Niemann-Pick Type C with Initial Crohn\u2019s Disease-like Presentation: Genotype-Phenotype Correlation Study"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-6489","authenticated-orcid":false,"given":"Bilal","family":"Azab","sequence":"first","affiliation":[{"name":"Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA"},{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Rabab\u2019h","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunia","family":"Aburizeg","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hashim","family":"Mohammad","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zain","family":"Dardas","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Mustafa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruba A.","family":"Khasawneh","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology and Nuclear Medicine, Faculty of Medicine King Abdullah University Hospital, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3050-136X","authenticated-orcid":false,"given":"Heyam","family":"Awad","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology and Forensic Medicine, School of Medicine, The University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-8985","authenticated-orcid":false,"given":"Ma\u2019mon M.","family":"Hatmal","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, The Hashemite University, Zarqa 13133, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-1553","authenticated-orcid":false,"given":"Eyad","family":"Altamimi","sequence":"additional","affiliation":[{"name":"Pediatric Department, Faculty of Medicine, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1097\/00062752-200001000-00009","article-title":"Niemann\u2013Pick Disease","volume":"7","author":"Kolodny","year":"2000","journal-title":"Curr Opin Hematol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ymgme.2015.05.013","article-title":"Successful within-patient dose escalation of olipudase alfa in acid sphingomyelinase deficiency","volume":"116","author":"Wasserstein","year":"2015","journal-title":"Mol. 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