{"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":1780760378009,"version":"3.54.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T00:00:00Z","timestamp":1642550400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Hermansky-Pudlak syndrome (HPS), a rare heterogeneous autosomal recessive disorder, is characterized by oculocutaneous albinism (OCA) and a bleeding diathesis due to a defect regarding melanosomes and platelet delta (\u03b4)-granule secretion. Interestingly, patients with HPS type 2 (HPS-2) or HPS type 10 (HPS-10) present additionally with an immunological defect. We investigated three patients (IP1, IP2, and IP3) who suffer from a bleeding diathesis. Platelet aggregometry showed impaired platelet function and flow cytometry revealed a severely reduced platelet CD63 expression hinting to either a defect of platelet delta granule secretion or a decreased number of delta granules in these patients. However, only IP3 presents with an apparent OCA. We performed panel sequencing and identified a homozygous deletion of exon 6 in <jats:italic>DTNBP1<\/jats:italic> for IP3<jats:italic>.<\/jats:italic> Western analysis confirmed the absence of the encoded protein dysbindin confirming the diagnosis of HPS-7. Interestingly, this patient reported additionally recurrent bacterial infections. Analysis of lymphocyte cytotoxicity showed a slightly reduced NK-degranulation previously documented in a more severe form in patients with HPS-2 or HPS-10. IP1 is carrier of two compound heterozygous variants in the <jats:italic>HPS3<\/jats:italic> gene (c.65C &amp;gt; G and c.1193G &amp;gt; A). A homozygous variant in <jats:italic>HPS5<\/jats:italic> (c.760G &amp;gt; T) was identified in IP2. The novel missense variants were classified as VUS (variant of uncertain significance) according to ACMG guidelines. For IP1 with the compound heterozygous variants in <jats:italic>HPS3<\/jats:italic> a specialized ophthalmological examination showed ocular albinism. <jats:italic>HPS3<\/jats:italic> and <jats:italic>HPS5<\/jats:italic> encode subunits of the BLOC-2 complex and patients with HPS-3 or HPS-5 are known to present with variable\/mild hypopigmentation.<\/jats:p>","DOI":"10.3389\/fphar.2021.786937","type":"journal-article","created":{"date-parts":[[2022,1,19]],"date-time":"2022-01-19T05:22:13Z","timestamp":1642569733000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Hermansky-Pudlak Syndrome: Identification of Novel Variants in the Genes HPS3, HPS5, and DTNBP1 (HPS-7)"],"prefix":"10.3389","volume":"12","author":[{"given":"Doris","family":"Boeckelmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mira","family":"Wolter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Neubauer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Sobotta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonia","family":"Lenz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Glonnegger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"K\u00e4smann-Kellner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Mann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Ehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Zieger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"997","DOI":"10.1182\/blood-2015-09-671636","article-title":"Mutations in AP3D1 Associated with Immunodeficiency and Seizures Define a New Type of Hermansky-Pudlak Syndrome","volume":"127","author":"Ammann","year":"2016","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1038\/ng576","article-title":"Mutation of a New Gene Causes a Unique Form of Hermansky-Pudlak Syndrome in a Genetic Isolate of central Puerto Rico","volume":"28","author":"Anikster","year":"2001","journal-title":"Nat. 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