{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T22:13:53Z","timestamp":1788473633276,"version":"build-2803163510"},"reference-count":14,"publisher":"Walter de Gruyter GmbH","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2021-0052_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Niemann\u2013Pick type C (NPC) disease is a rare progressive neurodegenerative condition that is characterized by the accumulation of cholesterol, glycosphingolipids, and sphingosine in lysosomes. Patients have various systemic and neurological findings depending on their age at onset. This disease is caused by the autosomal recessive transmission of mutations in the <jats:italic>NPC1<\/jats:italic> and <jats:italic>NPC2<\/jats:italic> genes; patients have mutations mainly in the <jats:italic>NPC1<\/jats:italic> gene (95%) and\u00a0the majority of them are point mutations located in the exonic regions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2021-0052_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>Here, we presented three cousins with hepatosplenomegaly and progressive neurodegeneration who were diagnosed with visceral-neurodegenerative NPC disease. Their parents were relatives, and they had a history of sibling death with similar complaints. Bone marrow smear showed foamy cells in patient 1. Vertical supranuclear gaze palsy was not present in all cases. Sphingomyelinase (SM) activities were almost normal to exclude NPA or NPB. Filipin staining was performed in patient 2 and showed a massive accumulation of unesterified cholesterol The <jats:italic>NPC1<\/jats:italic> gene analysis of the three patients showed a novel homozygous c.1553+5G&gt;A intronic mutation. cDNA analysis was performed from the patient 3 and both parents. It was observed that exon 9 was completely skipped in the homozygous mutant baby. Both the normal and the exon 9-skipped transcripts have been detected in the parents.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2021-0052_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>When combined with the filipin staining and the patients\u2019 clinical outcomes, this mutation is likely to be deleterious. Moreover, cDNA sequencing supports the pathogenicity of this novel variant.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2021-0052","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T21:21:34Z","timestamp":1639084894000},"page":"535-541","source":"Crossref","is-referenced-by-count":3,"title":["Niemann\u2013Pick type C disease with a novel intronic mutation: three Turkish cases from the same family"],"prefix":"10.1515","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6769-667X","authenticated-orcid":false,"given":"Gonca","family":"K\u0131l\u0131\u00e7 Y\u0131ld\u0131r\u0131m","sequence":"first","affiliation":[{"name":"Division of Child Nutrition and Metabolism, Department of Paediatrics , Faculty of Medicine, Eskisehir Osmangazi University , Eskisehir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-4578","authenticated-orcid":false,"given":"Co\u015fkun","family":"Yarar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Neurology, Department of Paediatrics , Faculty of Medicine, Eskisehir Osmangazi University , Eskisehir , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0425-0341","authenticated-orcid":false,"given":"Berna","family":"\u015eeker Y\u0131lmaz","sequence":"additional","affiliation":[{"name":"UCL Institute of Child Health, Genetics and Genomics Medicine , London , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2786-1911","authenticated-orcid":false,"given":"Serdar","family":"Ceylaner","sequence":"additional","affiliation":[{"name":"Intergen Genetics Centre , Ankara , Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"2023033123535395799_j_jpem-2021-0052_ref_001","doi-asserted-by":"crossref","unstructured":"McKay Bounford, K, Gissen, P. 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Hum Mutat 2003;22:313\u201325. https:\/\/doi.org\/10.1002\/humu.10255.","DOI":"10.1002\/humu.10255"},{"key":"2023033123535395799_j_jpem-2021-0052_ref_006","doi-asserted-by":"crossref","unstructured":"Di Leo, E, Panico, F, Tarugi, P, Battisti, C, Federico, A, Calandra, S. A point mutation in the lariat branch point of intron 6 of NPC1 as the cause of abnormal pre-mRNA splicing in Niemann-Pick type C disease. Hum Mutat 2004;24:440\u20138. https:\/\/doi.org\/10.1002\/humu.9287.","DOI":"10.1002\/humu.9287"},{"key":"2023033123535395799_j_jpem-2021-0052_ref_007","doi-asserted-by":"crossref","unstructured":"Millat, G, Mar\u00e7ais, C\u00b8 Tomasetto, C, Chikh, K, Fensom, AH, Harzer, K, et al.. Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop. Am J Hum Genet 2001;68:1373\u201385. https:\/\/doi.org\/10.1086\/320606.","DOI":"10.1086\/320606"},{"key":"2023033123535395799_j_jpem-2021-0052_ref_008","doi-asserted-by":"crossref","unstructured":"Sun, X, Marks, DL, Park, WD, Wheatley, CL, Puri, V, O\u2019Brien, JF, et al.. Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1. Am J Hum Genet 2001;68:1361\u201372. https:\/\/doi.org\/10.1086\/320599.","DOI":"10.1086\/320599"},{"key":"2023033123535395799_j_jpem-2021-0052_ref_009","doi-asserted-by":"crossref","unstructured":"Fernandez-Valero, EM, Ballart, A, Iturriaga, C, Lluch, M, Macias, J, Vanier, MT, et al.. Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations. 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J Lipid Res 2019;60:1410\u201324. https:\/\/doi.org\/10.1194\/jlr.ra119000157.","DOI":"10.1194\/jlr.RA119000157"},{"key":"2023033123535395799_j_jpem-2021-0052_ref_012","doi-asserted-by":"crossref","unstructured":"Mazzacuva, F, Mills, P, Mills, K, Camuzeaux, S, Gissen, P, Nicoli, ER, et al.. Identification of novel bile acids as biomarkers for the early diagnosis of Niemann-Pick C disease. FEBS Lett 2016;590:1651\u201362. https:\/\/doi.org\/10.1002\/1873-3468.12196.","DOI":"10.1002\/1873-3468.12196"},{"key":"2023033123535395799_j_jpem-2021-0052_ref_013","doi-asserted-by":"crossref","unstructured":"Ory, DS, Ottinger, EA, Farhat, NY, King, KA, Jiang, X, Weissfeld, L, et al.. Intrathecal 2-hydroxypropyl-betacyclodextrin decreases neurological disease progression in Niemann-Pick disease, type C1: a non-randomised, open-label, phase 1-2 trial. 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