Interstitial lung diseases (ILDs) are a very heterogeneous group of diseases. Although the aetiology of many of these diseases is not fully understood, an association with specific pathogenic gene variants has been demonstrated for some of the diseases. The aim of this review is to provide genotype-phenotype correlation information on monogenic ILDs to provide guidance to pulmonologists on when to refer ILD patients for genetic testing. Most patients with monogenic ILDs suffer from multiorgan involvement and should be managed by a multidisciplinary team of specialists. Different syndromes are associated with a greater risk of (nonrespiratory) malignancies (Birt-Hogg-Dubé syndrome and telomeropathies). Isolated lung involvement has been described in surfactant-related gene variant carriers (SFTPA 1 and 2, SFTPC) and patients with pulmonary alveolar microlithiasis. The clinical suspicion of monogenic ILDs should be raised in young patients diagnosed with ILD, patients with a known family history of ILD or suspected telomeropathies, and patients suspected of having syndromes associated with ILD. Patients with suspected monogenic ILDs should be aware of the possibility of genetic counselling both to obtain a diagnosis and to select further follow-up by pulmonologists and other involved specialists. Raising awareness of monogenic ILDs and creating counselling platforms is necessary both to diagnose and manage patients with these rare diseases.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

GATA-2 deficiency was recently described as common cause of overlapping syndromes of immunodeficiency, lymphedema, familiar myelodysplastic syndrome or acute myeloid leukemia. The aim of our study was to analyze bone marrow and peripheral blood samples of children with myelodysplastic syndrome or aplastic anemia to define prevalence of the GATA2 mutation and to assess whether mutations in GATA-2 transcription factor exhibit specific immunophenotypic features. The prevalence of a GATA2 mutation in a consecutively diagnosed cohort of children was 14% in advanced forms of myelodysplastic syndrome (refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and myelodysplasia-related acute myeloid leukemia), 17% in refractory cytopenia of childhood, and 0% in aplastic anemia. In GATA-2-deficient cases, we found the most profound B-cell lymphopenia, including its progenitors in blood and bone marrow, which correlated with significantly diminished intronRSS-Kde recombination excision circles in comparison to other myelodysplastic syndrome/aplastic anemia cases. The other typical features of GATA-2 deficiency (monocytopenia and natural killer cell lymphopenia) were less discriminative. In conclusion, we suggest screening for GATA2 mutations in pediatric myelodysplastic syndrome, preferentially in patients with impaired B-cell homeostasis in bone marrow and peripheral blood (low number of progenitors, intronRSS-Kde recombination excision circles and naïve cells).

• MeSH
• aplastická anemie diagnóza   etiologie   MeSH
• B-lymfocyty metabolismus   MeSH
• biologické markery MeSH
• buňky kostní dřeně metabolismus   patologie   MeSH
• diferenciální diagnóza MeSH
• dítě MeSH
• fenotyp MeSH
• imunofenotypizace MeSH
• kojenec MeSH
• kostní dřeň metabolismus   patologie   MeSH
• lidé MeSH
• lymfopenie diagnóza   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mutace MeSH
• myelodysplastické syndromy diagnóza   genetika   MeSH
• myeloidní buňky metabolismus   MeSH
• počet lymfocytů MeSH
• předškolní dítě MeSH
• prekurzorové B-lymfoidní buňky metabolismus   MeSH
• ROC křivka MeSH
• T-lymfocyty - podskupiny imunologie   metabolismus   MeSH
• transkripční faktor GATA2 nedostatek   MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• transkripční faktor GATA2 MeSH