First familial cases of type 2 congenital erythrocytosis (ECYT2) with a Chuvash pathogenic variant in gene in Poland: example of the clinical utility of next-generation sequencing in diagnostics of orphan diseases

In this article, we report familial cases of type 2 congenital erythrocytosis (ECYT2) in two siblings, a 2-year-old boy and his younger sister. Both patients were diagnosed based on laboratory findings including erythrocytosis, elevated hemoglobin levels, and hematocrit. Acquired erythrocytosis was excluded based on the clinical features and genetic analysis of genes. Next-generation sequencing was employed for older brother revealing NM_000551.4: c.598C>T, p.Arg200Trp homozygous variant in the gene, the similar variant was detected in the younger sibling. Sequencing analysis confirmed the c.598C>T heterozygous variant in both parents. To the best of our knowledge, these are the first confirmed cases of familial erythrocytosis type 2, also known as Chuvash type, in Poland

Results of Polish Adult Leukemia Study Group (PALG) project assessing TP53 mutations with next-generation sequencing technology in relapsed and refractory chronic lymphocytic leukemia patients — an 18-month update

Indtroduction and methods: In chronic lymphocytic leukemia (CLL), molecular and cytogenetic diagnostics are crucial for the determination of accurate prognosis and treatment choice. Among different genetic aberrations, del(17p13) or TP53 mutations constitute high-risk factors, and early identification of such defects is a high priority for CLL patients. While cytogenetic diagnostics is well-established and accessible for the majority of CLL patients in Poland, molecular diagnostics of TP53 mutations is performed only in a few ERIC-certified centers (eight as of September 2020), and only two of these employ next-generation sequencing (NGS) for routine analysis of TP53 status in CLL patients. Here we report the interim results of a project assessing TP53 mutations with NGS technology in relapsed or refractory CLL patients with confirmed negative del(17p13) status. 249 patients from 32 clinical centers were included in the study. Results: NGS analysis revealed TP53 mutations in 42/249 (17%) patients, half of whom (21/249, 8.5%) had subclonal mutations (VAF ≤10%). These results are in line with published data in relapsed/refractory CLL patients. Conclusions: The results of the project demonstrated the feasibility and accuracy of NGS testing in CLL patients despite several initial logistical and technical obstacles. Our study also proved that, with appropriate funding, CLL patients from any hematological center in Poland can have access to state-of-the-art molecular diagnostic