{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T15:39:35Z","timestamp":1780760375452,"version":"3.54.1"},"reference-count":16,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T00:00:00Z","timestamp":1571184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009553","name":"Agentura Pro Zdravotnick\u00fd V\u00fdzkum \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["16-29447A"],"award-info":[{"award-number":["16-29447A"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006435","name":"Central European Institute of Technology","doi-asserted-by":"publisher","award":["LQ1601"],"award-info":[{"award-number":["LQ1601"]}],"id":[{"id":"10.13039\/501100006435","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010653","name":"Masarykova Univerzita","doi-asserted-by":"publisher","award":["MUNI\/A\/1105\/2018"],"award-info":[{"award-number":["MUNI\/A\/1105\/2018"]}],"id":[{"id":"10.13039\/501100010653","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Pulm Med"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diathesis, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes. Homozygous or compound heterozygous pathological variants in <jats:italic>HPS1, HPS3, HPS4,<\/jats:italic> and several other genes lead to clinical manifestation of the disease.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>A 57-year-old female was admitted with congenital oculocutaneous albinism, thrombocytopathy and late-onset accelerated pulmonary fibrosis (first symptoms from age 50 onwards). Chest high-resolution computed tomography identified thickening of peribronchovascular interstitium, bronchiectasis, reticulations, honeycombing, ground glass opacities and lung parenchyma consolidations. HPS was clinically suspected. We performed whole exome sequencing (WES), a form of massive parallel sequencing, of proband-parents trio. Whole exome libraries were processed using KAPA Hyper Prep Kit, SeqCap EZ MedExome Enrichment Kit and HyperCap Bead Kit according to the SeqCap EZ HyperCap Workflow. The paired-end 2\u2009\u00d7\u200975 bp sequencing was performed on the Illumina NextSeq 500 Sequencer (Illumina Inc., USA). Furthermore, obtained variants by WES were evaluated using a virtual panel of genes: <jats:italic>HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3,<\/jats:italic> and <jats:italic>PLDN<\/jats:italic>. We identified a compound heterozygous genotype in <jats:italic>HPS1<\/jats:italic> gene in the proband. We identified a pathogenic frameshift variant c.1189delC; p.(Gln397Serfs*2), resulting in a premature stop codon. This variant has been previously associated with HPS. Furthermore, we characterized previously undescribed nonsense variant c.1507C\u2009&gt;\u2009T; p.(Gln503*), resulting in a premature stop codon and mRNA degradation through nonsense-mediated decay. Sanger sequencing validated the presence of both variants and simultaneously confirmed the heterozygous carrier status of parents. Unfortunately, the patient died due to fulminant progression of pulmonary fibrosis 2\u2009months after diagnostics.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Compound heterozygous mutations in <jats:italic>HPS1<\/jats:italic> in the proband lead to disruption of <jats:italic>HPS1<\/jats:italic> gene and clinical manifestation of HPS with severe pulmonary fibrosis. This case illustrates the need to consider HPS in differential diagnostics of pulmonary fibrosis. Pulmonary fibrosis is a common cause of death in HPS patients. Earlier diagnosis may enable better treatment for these patients.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12890-019-0941-4","type":"journal-article","created":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T10:03:55Z","timestamp":1571220235000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report"],"prefix":"10.1186","volume":"19","author":[{"given":"Martina","family":"Doubkov\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Trizuljak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"Vrzalov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Hrazdirov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivona","family":"Blah\u00e1kov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lenka","family":"Radov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u0160\u00e1rka","family":"Posp\u00ed\u0161ilov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1269-6282","authenticated-orcid":false,"given":"Michael","family":"Doubek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,10,16]]},"reference":[{"key":"941_CR1","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1146\/annurev.genom.9.081307.164303","volume":"9","author":"M Huizing","year":"2008","unstructured":"Huizing M, Helip-Wooley A, Westbroek W, Gunay-Aygun M, Gahl WA. Disorders of lysosome-related organelle biogenesis: clinical and molecular genetics. Annu Rev Genomics Hum Genet. 2008;9:359\u201386.","journal-title":"Annu Rev Genomics Hum Genet"},{"issue":"18","key":"941_CR2","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1056\/NEJM199804303381803","volume":"338","author":"WA Gahl","year":"1998","unstructured":"Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, et al. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998;338(18):1258\u201364.","journal-title":"N Engl J Med"},{"key":"941_CR3","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1136\/thoraxjnl-2018-211920","volume":"73","author":"OJ McElvaney","year":"2018","unstructured":"McElvaney OJ, Huizing M, Gahl WA, O\u2019Donovan P, Horan D, Logan PM, et al. 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