BACKGROUND: 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 HPS1, HPS3, HPS4, and several other genes lead to clinical manifestation of the disease. CASE PRESENTATION: 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 × 75 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: HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, and PLDN. We identified a compound heterozygous genotype in HPS1 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 > T; 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 months after diagnostics. CONCLUSIONS: Compound heterozygous mutations in HPS1 in the proband lead to disruption of HPS1 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.

• Klíčová slova
• Exome sequencing, Hermansky-Pudlak syndrome, Pulmonary fibrosis,
• MeSH
• fatální výsledek MeSH
• Heřmanského-Pudlákův syndrom * diagnóza   genetika   patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mutace MeSH
• plíce diagnostické zobrazování   patologie   MeSH
• plicní fibróza * diagnóza   genetika   patofyziologie   MeSH
• počítačová rentgenová tomografie metody   MeSH
• progrese nemoci MeSH
• sekvenování exomu metody   MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• HPS1 protein, human MeSH Prohlížeč
• membránové proteiny MeSH

BACKGROUND: Chromosomal duplications involving 17p13.3 have recently been defined as a new distinctive syndrome with several diagnosed patients. Some variation is known to occur in the breakpoints of the duplicated region and, consequently, in the phenotype as well. AIMS: We report on a patient, the fifth to our knowledge, a 4-year-old girl with a pure de novo subtelomeric 17p13.2-pter duplication. She presents all of the facial features described so far for this duplication and in addition, a unilateral palmar transversal crease and oculocutaneous albinism which has not been reported previously. METHODS: A detailed molecular description of the reported aberration and correlation with the observed phenotypical features based on a literature review. We discuss the possible molecular etiology of albinism in regard to the mode of inheritance. CONCLUSION: The new data provided here may be useful for further genotype correlations in syndromes with oculocutaneous albinism, especially of autosomal dominant inheritance.

• Klíčová slova
• 17p13.3, albinism, chromosomal duplication,
• MeSH
• albinismus generalizovaný genetika   MeSH
• duplikace chromozomů genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• lidé MeSH
• lidské chromozomy, pár 19 genetika   MeSH
• předškolní dítě MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

The cellular prion protein (PrPc) is a membrane glycoprotein expressed on many human cells including platelets. We investigated the cellular localization of platelet PrPc. In resting platelets most PrPc was localized inside the cells. The correlation of PrPc and P-selectin surface up-regulation after platelet activation suggested its association with alpha-granules. This was confirmed by normal expression of PrPc on Hermansky-Pudlak syndrome platelets, which lack dense granules, and failure of gray platelet syndrome platelets, which lack alpha-granules, to up-regulate PrPc. Our results warrant further studies on the role of platelet PrPc in the transmission of prion diseases by blood transfusion.

• MeSH
• Creutzfeldtova-Jakobova nemoc krev   přenos   MeSH
• cytoplazmatická granula chemie   ultrastruktura   MeSH
• Heřmanského-Pudlákův syndrom krev   MeSH
• lidé MeSH
• potransfuzní reakce * MeSH
• priony krev   MeSH
• PrPC proteiny krev   MeSH
• trombocyty chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• priony MeSH
• PrPC proteiny MeSH