PT  - JOURNAL ARTICLE
AU  - Martina Doubková
AU  - Jakub Trizuljak
AU  - Anna Hrazdirová
AU  - Zuzana Vrzalová
AU  - Ivona Blaháková
AU  - Lenka Radová
AU  - Šárka Pospíšilová
AU  - Michael Doubek
TI  - A rare diagnosis: Hermansky-Pudlak syndrome in a patient with pulmonary fibrosis, oculocutaneous albinism and thrombocytopathy
AID  - 10.1183/13993003.congress-2019.PA1400
DP  - 2019 Sep 28
TA  - European Respiratory Journal
PG  - PA1400
VI  - 54
IP  - suppl 63
4099  - http://erj.ersjournals.com/content/54/suppl_63/PA1400.short
4100  - http://erj.ersjournals.com/content/54/suppl_63/PA1400.full
SO  - Eur Respir J2019 Sep 28; 54
AB  - Hermansky-Pudlak Syndrome (HPS) is an autosomal recessive disorder associated with oculocutaneous albinism, bleeding diathesis, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes. Homozygous or compound heterozygous mutations in HPS1, HPS3, HPS4 and several other genes lead to clinical manifestation of the disease.A 57-year-old patient with congenital oculocutaneous albinism, thrombocytopathy and late onset pulmonary fibrosis was referred to our clinic. Negative family history of these symptoms suggested autosomal-recessive mode of inheritance. We performed NGS analysis of proband-parents trio. Whole-exome libraries were prepared according to the Nimblegen SeqCap EZ Exome v3 protocol and sequencing was performed on NextSeq 500 for all of them. Furthermore, we performed in silico analysis of a virtual gene panel, including HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, and PLDN.Whole-exome sequencing identified a compound heterozygous genotype in HPS1 gene in the proband: 1) a pathogenic frameshift variant c.1189delC (p.Gln397Serfs*2), resulting in a premature stop codon, associated with HPS, and 2) previously undescribed nonsense variant, c. 1507C>T (p.Gln503*), resulting in a premature stop and mRNA degradation. Presence of both variants was verified by Sanger sequencing. The following molecular-genetic analysis of parents confirmed their heterozygous carrier status.Compound heterozygous mutations in HPS1 in the proband lead to clinical manifestation of HPS with severe pulmonary fibrosis. This study was supported by the grant AZV 16-29447A.FootnotesCite this article as: European Respiratory Journal 2019; 54: Suppl. 63, PA1400.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).