A rare diagnosis: Hermansky-Pudlak syndrome in a patient with pulmonary fibrosis, oculocutaneous albinism and thrombocytopathy

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F19%3A00071644" target="_blank" >RIV/65269705:_____/19:00071644 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/19:00108576

Result on the web

<a href="https://erj.ersjournals.com/content/54/suppl_63/PA1400" target="_blank" >https://erj.ersjournals.com/content/54/suppl_63/PA1400</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1183/13993003.congress-2019.PA1400" target="_blank" >10.1183/13993003.congress-2019.PA1400</a>

Result language

angličtina

Original language name

A rare diagnosis: Hermansky-Pudlak syndrome in a patient with pulmonary fibrosis, oculocutaneous albinism and thrombocytopathy

Original language description

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&gt;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.

Czech name

—

Czech description

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Type

O - Miscellaneous

CEP classification

—

OECD FORD branch

10608 - Biochemistry and molecular biology

Project

<a href="/en/project/NV16-29447A" target="_blank" >NV16-29447A: Searching for mutations predisposing to familial hematologic and oncologic diseases</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů