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

Kód výsledku v 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>

Nalezeny alternativní kódy

RIV/00216224:14110/19:00108576

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NV16-29447A" target="_blank" >NV16-29447A: Vyhledávání mutací predisponujících k familiárním hematologickým a onkologickým onemocněním</a><br>

Návaznosti

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

Rok uplatnění

2019

Kód důvěrnosti údajů

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