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@article{1574756,
author = {Doubková, Martina and Trizuljak, Jakub and Vrzalová, Zuzana and Hrazdirová, Anna and Blaháková, Ivona and Radová, Lenka and Pospíšilová, Šárka and Doubek, Michael},
article_location = {London},
article_number = {1},
doi = {http://dx.doi.org/10.1186/s12890-019-0941-4},
keywords = {Exome sequencing; Hermansky-Pudlak syndrome; Pulmonary fibrosis},
language = {eng},
issn = {1471-2466},
journal = {BMC Pulmonary Medicine},
title = {Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report},
url = {https://bmcpulmmed.biomedcentral.com/track/pdf/10.1186/s12890-019-0941-4},
volume = {19},
year = {2019}
}
TY - JOUR
ID - 1574756
AU - Doubková, Martina - Trizuljak, Jakub - Vrzalová, Zuzana - Hrazdirová, Anna - Blaháková, Ivona - Radová, Lenka - Pospíšilová, Šárka - Doubek, Michael
PY - 2019
TI - Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report
JF - BMC Pulmonary Medicine
VL - 19
IS - 1
SP - 178
EP - 178
PB - Biomed Central LTD
SN - 14712466
KW - Exome sequencing
KW - Hermansky-Pudlak syndrome
KW - Pulmonary fibrosis
UR - https://bmcpulmmed.biomedcentral.com/track/pdf/10.1186/s12890-019-0941-4
L2 - https://bmcpulmmed.biomedcentral.com/track/pdf/10.1186/s12890-019-0941-4
N2 - 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 x 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.
ER -
DOUBKOVÁ, Martina, Jakub TRIZULJAK, Zuzana VRZALOVÁ, Anna HRAZDIROVÁ, Ivona BLAHÁKOVÁ, Lenka RADOVÁ, Šárka POSPÍŠILOVÁ a Michael DOUBEK. Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report. \textit{BMC Pulmonary Medicine}. London: Biomed Central LTD, roč.~19, č.~1, s.~178-183. ISSN~1471-2466. doi:10.1186/s12890-019-0941-4. 2019.
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