Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome
with fulminant progression of pulmonary fibrosis: a case report

J 2019

Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report

DOUBKOVÁ, Martina, Jakub TRIZULJAK, Zuzana VRZALOVÁ, Anna HRAZDIROVÁ, Ivona BLAHÁKOVÁ et. al.

Základní údaje

Originální název

Novel genetic variant of HPS1 gene in Hermansky-Pudlak syndrome with fulminant progression of pulmonary fibrosis: a case report

Autoři

DOUBKOVÁ, Martina (203 Česká republika, domácí), Jakub TRIZULJAK (703 Slovensko, domácí), Zuzana VRZALOVÁ (203 Česká republika, domácí), Anna HRAZDIROVÁ (203 Česká republika, domácí), Ivona BLAHÁKOVÁ (203 Česká republika, domácí), Lenka RADOVÁ (203 Česká republika, domácí), Šárka POSPÍŠILOVÁ (203 Česká republika, domácí) a Michael DOUBEK (203 Česká republika, garant, domácí)

Vydání

BMC Pulmonary Medicine, London, Biomed Central LTD, 2019, 1471-2466

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30203 Respiratory systems

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 2.813

Kód RIV

RIV/00216224:14740/19:00108528

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1186/s12890-019-0941-4

UT WoS

000490720400003

Klíčová slova anglicky

Exome sequencing; Hermansky-Pudlak syndrome; Pulmonary fibrosis

Štítky

14110215, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 10. 2024 09:12, Ing. Martina Blahová

Anotace

V originále

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.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

MUNI/A/1105/2018, interní kód MU

Název: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VI (Akronym: VýDiTeHeMA VI)

Investor: Masarykova univerzita, Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VI, DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

NV16-29447A, projekt VaV

Název: Vyhledávání mutací predisponujících k familiárním hematologickým a onkologickým onemocněním

90091, velká výzkumná infrastruktura

Název: NCMG

Citovat

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. BMC Pulmonary Medicine. London: Biomed Central LTD, 2019, roč. 19, č. 1, s. 178-183. ISSN 1471-2466. Dostupné z: https://dx.doi.org/10.1186/s12890-019-0941-4.

@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, 2019, roč.~19, č.~1, s.~178-183. ISSN~1471-2466. Dostupné z: https://dx.doi.org/10.1186/s12890-019-0941-4.

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