{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:40:30Z","timestamp":1780760430190,"version":"3.54.1"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,10,4]],"date-time":"2019-10-04T00:00:00Z","timestamp":1570147200000},"content-version":"am","delay-in-days":365,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#am"},{"start":{"date-parts":[[2018,10,4]],"date-time":"2018-10-04T00:00:00Z","timestamp":1538611200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000053","name":"National Eye Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000179","name":"Office of the Director","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000179","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:p>He\u0159mansk\u00fd\u2013Pudl\u00e1k syndrome (HPS), a rare autosomal recessive disorder, manifests with oculocutaneous albinism and a bleeding diathesis. However, severity of disease can be variable and is typically related to the genetic subtype of HPS; HPS type 6 (HPS\u20106) is an uncommon subtype generally associated with mild disease. A Caucasian adult female presented with a history of severe bleeding; ophthalmologic examination indicated occult oculocutaneous albinism. The patient was diagnosed with a platelet storage pool disorder, and platelet whole mount electron microscopy demonstrated absent delta granules. Genome\u2010wide SNP analysis showed regions of homozygosity that included the <jats:italic>HPS1<\/jats:italic> and <jats:italic>HPS6<\/jats:italic> genes. Full length <jats:italic>HPS1<\/jats:italic> transcript was amplified by PCR of genomic DNA. Targeted next\u2010generation sequencing identified a novel homozygous missense variant in <jats:italic>HPS6<\/jats:italic> (c.383\u2009T\u2009&gt;\u2009C; p.V128A); this was associated with significantly reduced <jats:italic>HPS6<\/jats:italic> mRNA and protein expression in the patient's fibroblasts compared to control cells. These findings highlight the variable severity of disease manifestations in patients with HPS, and illustrate that HPS can be diagnosed in patients with excessive bleeding and occult oculocutaneous albinism. Genetic analysis and platelet electron microscopy are useful diagnostic tests in evaluating patients with suspected HPS.<\/jats:p><jats:p>Clinical Trial registration:<\/jats:p><jats:p>Registrar: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link><\/jats:p><jats:p>Website: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">www.clinicaltrials.gov<\/jats:ext-link><\/jats:p><jats:p>Registration Numbers: NCT00001456 and NCT00084305.<\/jats:p>","DOI":"10.1002\/ajmg.a.40514","type":"journal-article","created":{"date-parts":[[2018,10,28]],"date-time":"2018-10-28T18:44:14Z","timestamp":1540752254000},"page":"2819-2823","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Severe bleeding with subclinical oculocutaneous albinism in a patient with a novel <i>HPS6<\/i> missense variant"],"prefix":"10.1002","volume":"176","author":[{"given":"Chen G.","family":"Han","sequence":"first","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin J.","family":"O'Brien","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea M.","family":"Coon","sequence":"additional","affiliation":[{"name":"Division of Hematopathology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Majerus","sequence":"additional","affiliation":[{"name":"Division of Hematopathology Mayo Clinic  Rochester Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laryssa A.","family":"Huryn","sequence":"additional","affiliation":[{"name":"Ophthalmic Genetics and Visual Function Branch National Eye Institute, National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara G.","family":"Haroutunian","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagabhishek","family":"Moka","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Internal Medicine, Quillen College of Medicine East Tennessee State University  Johnson City Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy J.","family":"Introne","sequence":"additional","affiliation":[{"name":"Office of the Clinical Director National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen","family":"Macnamara","sequence":"additional","affiliation":[{"name":"NIH Undiagnosed Diseases Program, Common Fund, Office of the Director National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William A.","family":"Gahl","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland"},{"name":"Office of the Clinical Director National Human Genome Research Institute, National Institutes of Health  Bethesda Maryland"},{"name":"NIH Undiagnosed Diseases Program, Common Fund, Office of the Director National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"May Christine V.","family":"Malicdan","sequence":"additional","affiliation":[{"name":"Medical Genetics Branch National Human Genome 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