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.
- 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
Poruchy funkce krevních destiček (trombocytopatie) mohou být vrozené či získané. Vrozené trombocytopatie jsou vzácná onemocnění, spojená ve velké většině s krvácivou diatézou různé závažnosti. Jejich diagnostika je obtížná pro omezené spektrum a dostupnost vyšetřovacích metod. Získané trombocytopatie jsou výrazně častější a jsou buď spojeny s nejrůznějšími chorobnými stavy, nebo vyvolány léky, zejména protidestičkovou terapií.
Disorders of platelet function are both inherited and acquired. Inherited platelet disorders are rare diseases that are mostly cause of mild to severe bleeding diathesis. The diagnosis is difficult due to limited spectrum and availibility of laboratory assays. Acquired platelet disorders are far more common. They are associated with various disorders or with medications, notably with antiplatelet therapy.
- Klíčová slova
- VWD-destičkový typ (pseudo-VWD), syndrom lepivých destiček,
- MeSH
- Bernardův-Soulierův syndrom diagnóza MeSH
- Chediakův-Higashiho syndrom diagnóza terapie MeSH
- dědičné koagulopatie diagnóza farmakoterapie genetika patofyziologie terapie MeSH
- diferenciální diagnóza MeSH
- hematologické testy MeSH
- Heřmanského-Pudlákův syndrom diagnóza terapie MeSH
- inhibitory agregace trombocytů škodlivé účinky MeSH
- lidé MeSH
- syndrom šedých destiček diagnóza MeSH
- trombastenie diagnóza terapie MeSH
- trombocytopatie * diagnóza farmakoterapie patofyziologie terapie vrozené MeSH
- trombocyty fyziologie patologie MeSH
- Wiskottův-Aldrichův syndrom diagnóza terapie MeSH
- Check Tag
- lidé MeSH
- MeSH
- buňky cytologie patologie MeSH
- Heřmanského-Pudlákův syndrom klasifikace MeSH
- lidé MeSH
- neutrofily patologie ultrastruktura MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- albinismus generalizovaný MeSH
- Heřmanského-Pudlákův syndrom klasifikace patofyziologie patologie MeSH
- lidé MeSH
- lymfohistiocytóza hemofagocytární etiologie komplikace patofyziologie MeSH
- transplantace hematopoetických kmenových buněk využití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky 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
- albinismus MeSH
- Heřmanského-Pudlákův syndrom MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
