{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:39:38Z","timestamp":1780760378750,"version":"3.54.1"},"reference-count":14,"publisher":"Cold Spring Harbor Laboratory","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:p>Hermansky\u2013Pudlak syndrome (HPS) is a genetic disorder characterized by oculocutaneous albinism and variable pulmonary fibrosis, granulomatous colitis, or immunodeficiency. The diagnosis relies on clinical findings, platelet transmission electron microscopy studies showing absent dense granules, or the identification of a pathogenic genotype in one of 11 associated genes, including <jats:italic>HPS1<\/jats:italic>. We report a 2-wk-old male with significant iris transillumination defects, a pale fundus, and mild corectopia found by clinical exome sequencing to have a previously reported pathogenic variant, c.972dupC p.(Met325HisfsTer128), and a variant of uncertain significance, c.1846G&gt;A p.(Glu616Lys), in <jats:italic>HPS1<\/jats:italic>. To determine whether his phenotype was consistent with HPS, follow-up studies of whole blood lumiaggregometry and platelet transmission electron microscopy were performed that revealed absent or markedly reduced platelet ATP secretion and virtually absent platelet dense granules, thus confirming the diagnosis. To the best of our knowledge, our case is the first in which the c.1846G&gt;A p.(Glu616Lys) variant is identified in a patient with HPS. In addition, the case also highlights the importance of leveraging appropriate confirmatory clinical testing and reverse phenotyping, which allowed the care team to establish the clinical diagnosis of HPS and reclassify the previously reported variant of uncertain significance in <jats:italic>HPS1<\/jats:italic> to likely pathogenic.<\/jats:p>","DOI":"10.1101\/mcs.a006110","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T20:10:25Z","timestamp":1628280625000},"page":"a006110","source":"Crossref","is-referenced-by-count":4,"title":["A novel likely pathogenic variant in a patient with Hermansky\u2013Pudlak syndrome"],"prefix":"10.1101","volume":"7","author":[{"given":"Lisa A.","family":"Lansdon","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric T.","family":"Rush","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra","family":"Engleman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol J.","family":"Saunders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabor","family":"Oroszi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2021,8,6]]},"reference":[{"key":"2021112506241378000_7.5.a006110.1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0410-248"},{"key":"2021112506241378000_7.5.a006110.2","doi-asserted-by":"publisher","DOI":"10.1080\/09537104.2018.1476682"},{"key":"2021112506241378000_7.5.a006110.3","unstructured":"Huizing M , Malicdan MCV , Gochuico BR , Gahl WA . 1993. Hermansky\u2013Pudlak syndrome. In GeneReviews\u00ae (ed. Adam MP , Ardinger HH , Pagon RA , ). University of Washington, Seattle."},{"key":"2021112506241378000_7.5.a006110.4","doi-asserted-by":"publisher","DOI":"10.1002\/humu.23968"},{"key":"2021112506241378000_7.5.a006110.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2308-7"},{"key":"2021112506241378000_7.5.a006110.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng1196-300"},{"key":"2021112506241378000_7.5.a006110.7","doi-asserted-by":"publisher","DOI":"10.1086\/301757"},{"key":"2021112506241378000_7.5.a006110.8","doi-asserted-by":"publisher","DOI":"10.1111\/pcmr.12800"},{"key":"2021112506241378000_7.5.a006110.9","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-021-00835-9"},{"key":"2021112506241378000_7.5.a006110.10","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2021112506241378000_7.5.a006110.11","doi-asserted-by":"publisher","DOI":"10.1159\/000247258"},{"key":"2021112506241378000_7.5.a006110.12","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks539"},{"key":"2021112506241378000_7.5.a006110.13","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.2830260403"},{"key":"2021112506241378000_7.5.a006110.14","first-page":"1","article-title":"In vitro analysis of the hemostatic properties of whole blood products prepared with a platelet-sparing leukoreduction filter","volume":"4","year":"2018","journal-title":"J Thromb Circ Open Access"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a006110","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T14:24:26Z","timestamp":1637850266000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a006110"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,6]]},"references-count":14,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,10,19]]},"published-print":{"date-parts":[[2021,10]]}},"alternative-id":["10.1101\/mcs.a006110"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a006110","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,6]]}}}