{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T11:18:18Z","timestamp":1777288698851,"version":"3.51.4"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T00:00:00Z","timestamp":1711670400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Niemann\u2013Pick disease type C (NPC) is one of the lysosomal storage disorders. It is caused by biallelic pathogenic variants in\n                    <jats:italic>NPC1<\/jats:italic>\n                    or\n                    <jats:italic>NPC2<\/jats:italic>\n                    , which results in a defective cholesterol trafficking inside the late endosome and lysosome. There is a high clinical variability in the age of presentation and the phenotype of this disorder making the diagnosis challenging. Here, we report a patient with an infantile onset global developmental delay, microcephaly and dysmorphic features, homozygous for c.3560C&gt;T (p.A1187V) variant in\n                    <jats:italic>NPC1<\/jats:italic>\n                    . His plasma oxysterol levels were normal on two occasions. His lyso\u2010sphingomyelin\u2010509 (lyso\u2010SM 509) and urinary bile acid levels were normal. Based on the phenotype and biochemical features, the diagnosis of NPC was excluded in this patient. We emphasize the importance of functional characterization in the classification of novel variants to prevent a misdiagnosis. Matching the phenotype and biochemical evidence with the molecular genomic tests is crucial for the confirmation of genetic diagnoses.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.63595","type":"journal-article","created":{"date-parts":[[2024,3,29]],"date-time":"2024-03-29T03:29:11Z","timestamp":1711682951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Importance of the biochemical investigations for the functional characterization of a\n                    <scp>\n                      <i>NPC1<\/i>\n                    <\/scp>\n                    variant identified by exome sequencing"],"prefix":"10.1002","volume":"194","author":[{"given":"Nihal","family":"Almenabawy","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iveta","family":"Sosova","sequence":"additional","affiliation":[{"name":"Alberta Newborn Screening and Biochemical Genetics Laboratory University of Alberta Hospital, Alberta Precision Laboratories  Edmonton Alberta Canada"},{"name":"Department of Laboratory Medicine and Pathology University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8396-6764","authenticated-orcid":false,"given":"Saadet","family":"Mercimek\u2010Andrews","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Faculty of Medicine and Dentistry University of Alberta  Edmonton Alberta Canada"},{"name":"Women and Children's Health Research Institute, University of Alberta  Edmonton Alberta Canada"},{"name":"Neuroscience and Mental Health Institute, University of Alberta  Edmonton Alberta Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg025"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.11.005"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2021.06.011"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9030679"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2018.08.039"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-009-0175-3"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1711716114"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M093971"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.04.011"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12944-019-1088-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.03.012"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-020-01363-2"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2015.12.018"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2890"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2016.06.004"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2015.123"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63595","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.63595","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63595","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T07:28:42Z","timestamp":1771399722000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63595"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,29]]},"references-count":17,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2024,8]]}},"alternative-id":["10.1002\/ajmg.a.63595"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63595","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,29]]},"assertion":[{"value":"2023-12-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-29","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63595"}}