Inherited thrombocytopenias (ITs) encompass a group of rare disorders characterized by diminished platelet count. Recent advancements have unveiled various forms of IT, with inherited thrombocytopenia 2 (THC2) emerging as a prevalent subtype associated with germline variants in the critical 5' untranslated region of the ANKRD26 gene. This region is crucial in regulating the gene expression of ANKRD26, particularly in megakaryocytes. THC2 is an autosomal dominant disorder presenting as mild-to-moderate thrombocytopenia with minimal symptoms, with an increased risk of myeloproliferative malignancies. In our study of a family with suspected IT, three affected individuals harbored the c.-118C>T ANKRD26 variant, while four healthy members carried the c.-140C>G ANKRD26 variant. We performed a functional analysis by studying platelet-specific ANKRD26 gene expression levels using quantitative real-time polymerase-chain reaction. Functional analysis of the c.-118C>T variant showed a significant increase in ANKRD26 expression in affected individuals, supporting its pathogenicity. On the contrary, carriers of the c.-140C>G variant exhibited normal platelet counts and no significant elevation in the ANKRD26 expression, indicating the likely benign nature of this variant. Our findings provide evidence confirming the pathogenicity of the c.-118C>T ANKRD26 variant in THC2 and suggest the likely benign nature of the c.-140C>G variant.
- MeSH
- 5' nepřekládaná oblast * MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezibuněčné signální peptidy a proteiny MeSH
- rodokmen * MeSH
- trombocytopenie * genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: In contrast with the well-known and described deletion of the 22q11 chromosome region responsible for DiGeorge syndrome, 22q12 deletions are much rarer. Only a few dozen cases have been reported so far. This region contains genes responsible for cell cycle control, chromatin modification, transmembrane signaling, cell adhesion, and neural development, as well as several cancer predisposition genes. CASE PRESENTATION: We present a patient with cleft palate, sensorineural hearing loss, vestibular dysfunction, epilepsy, mild to moderate intellectual disability, divergent strabism, pes equinovarus, platyspondylia, and bilateral schwannoma. Using Microarray-based Comparative Genomic Hybridization (aCGH), we identified the de novo 3.8 Mb interstitial deletion at 22q12.1→22q12.3. We confirmed deletion of the critical NF2 region by MLPA analysis. DISCUSSION: Large 22q12 deletion in the proband encases the critical NF2 region, responsible for development of bilateral schwannoma. We compared the phenotype of the patient with previously reported cases. Interestingly, our patient developed cleft palate even without deletion of the MN1 gene, deemed responsible in previous studies. We also strongly suspect the DEPDC5 gene deletion to be responsible for seizures, consistent with previously reported cases.
- Publikační typ
- časopisecké články MeSH
- Klíčová slova
- poruchy krvetvorby,
- MeSH
- krevní nemoci * diagnóza genetika klasifikace vrozené MeSH
- leukemie diagnóza vrozené MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- systémová mastocytóza * diagnóza farmakoterapie imunologie klasifikace patofyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Bloom syndrome is an autosomal recessive disorder characterized by prenatal and postnatal growth deficiency, photosensitive skin changes, immune deficiency, insulin resistance, and a greatly increased risk of early-onset cancer and development of multiple malignancies. Loss-of-function variants of the BLM gene, which codes for a RecQ helicase, cause Bloom syndrome. We report a consanguineous family, with 2 siblings showing clinical signs of suspected chromosome breakage disorder. One of them developed recurrent malignant lymphoma during lifetime. We performed next-generation sequencing analysis, focusing on cancer predisposition syndromes. We identified a homozygous pathogenic nonsense variant c.1642C>T (p.Gln548*) in the BLM gene in the proband, associated with Bloom syndrome. Sanger sequencing validated the presence of a homozygous pathogenic variant in the proband and also in the brother with short stature. In this article, we will focus on the clinical presentation of the syndrome in this particular family as well as the characteristics of malignancies found in the proband.
- Publikační typ
- časopisecké články MeSH
BACKGROUND: In indolent systemic mastocytosis (ISM), several risk factors of disease progression have been identified. Previous studies, performed with limited patient numbers, have also shown that the clinical course in ISM is stable and comparable to that of cutaneous mastocytosis (CM). The aim of this project was to compare the prognosis of patients with ISM with that of patients with CM. METHODS: We employed a dataset of 1993 patients from the registry of the European Competence Network on Mastocytosis (ECNM) to compare outcomes of ISM and CM. RESULTS: We found that overall survival (OS) is worse in ISM compared to CM. Moreover, in patients with typical ISM, bone marrow mastocytosis (BMM), and smoldering SM (SSM), 4.1% of disease progressions have been observed (4.9% of progressions in typical ISM group, 1.7% in BMM, and 9.4% in SSM). Progressions to advanced SM were observed in 2.9% of these patients. In contrast, six patients with CM (1.7%) converted to ISM and no definitive progression to advanced SM was found. No significant differences in OS and event-free survival (EFS) were found when comparing ISM, BMM, and SSM. Higher risk of both progression and death was significantly associated with male gender, worse performance status, and organomegaly. CONCLUSION: Our data confirm the clinical impact of the WHO classification that separates ISM from CM and from other SM variants.
- MeSH
- chronická lymfatická leukemie * farmakoterapie MeSH
- cílená molekulární terapie * MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- monoklonální protilátky farmakologie terapeutické užití MeSH
- receptory antigenů B-buněk antagonisté a inhibitory terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- Klíčová slova
- Ibrutinib,
- MeSH
- chronická lymfatická leukemie * diagnóza patologie terapie MeSH
- lidé MeSH
- prognóza MeSH
- protinádorové látky klasifikace terapeutické užití MeSH
- protokoly protinádorové kombinované chemoterapie MeSH
- pyrazoly MeSH
- pyrimidiny MeSH
- recidiva MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- tyrosinkinasy antagonisté a inhibitory MeSH
- Check Tag
- lidé MeSH
