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Background Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy (LVH) in the absence of predisposing cardiovascular conditions. Pathogenic variants in at least 16 cardiac sarcomeric genes have been implicated in HCM, most of which act in a dominant‐negative fashion. However loss‐of‐function (haploinsufficiency) is the most common disease mechanism for pathogenic variants in MYBPC3, suggesting that MYBPC3 complete deletion may play a role in HCM pathogenesis. Here, we investigate MYBPC3 complete deletion as a disease mechanism in HCM by analyzing two unrelated patients with confirmed diagnosis of HCM that tested negative by Sanger sequencing analysis. Methods MYBPC3 complete deletion was investigated by Multiplex ligation‐dependent probe amplification (MLPA) and microarray analyses. The mechanism of deletion was investigated by interrogating the SINEBase database. Results Patient‐1 was diagnosed with nonobstructive HCM in his mid‐40s while undergoing assessment for palpitations, and patient‐2 with obstructive HCM in his late‐20s while undergoing systolic heart murmur assessment for an unrelated illness. MLPA testing revealed a heterozygous deletion of all MYBPC3 exons in both patients. Subsequent microarray testing confirmed these deletions which extended beyond the 5′ and 3′ ends of MYBPC3. Genomic assessment suggested that these deletions resulted from Alu/Alu‐homologous recombination. Conclusion Our results demonstrate that haploinsufficiency resulting from MYBPC3 complete deletion, potentially mediated by Alu recombination, is an important disease mechanism in cardiomyopathy and emphasizes the importance of copy number variation analysis in patients clinically suspected of HCM., We report on the complete deletion of MYBPC3, potentially mediated through Alu recombination, in two patients with confirmed diagnosis of hypertrophic cardiomyopathy (HCM). Our result demonstrates for the first time that MYBPC3 complete deletion is an important disease mechanism in cardiomyopathy and emphasizes the importance of copy number variation analysis in patients clinically suspected of HCM.

The detection of cytogenetic abnormalities in multiple myeloma (MM) has received more importance over last years for risk stratification and the new risk-adapted treatment strategies. Conventional G-banding analysis should be included in a routine procedure for the initial diagnostic workup for patients suspected of MM. However, the detection of chromosomal abnormalities in MM by conventional cytogenetics is limited owing to the low proliferative activity of malignant plasma cells as well as the low number of plasma cells in bone marrow specimens. Fluorescence in situ hybridization (FISH) or microarray-based technologies can overcome some of those drawbacks and detect specific target arrangements as well as chromosomal copy number changes. In this review, we will discuss different cytogenetic approaches and compare their strength and weakness to provide genetic information for risk stratification and prediction of outcome in MM patients.

[Figure][1] A 61-year-old woman presented with pancytopenia, hemoglobin 100 g/L, neutrophils 0.77 × 109/L, and platelets 50 × 109/L. Blood film showed a leukoerythroblastic picture with cytoplasmic vacuolated blasts. Marrow aspirate was dry tap, but touch preparations of the biopsy

Aims Lipoblastoma is a benign neoplasm of embryonic white fat tissue that results from the proliferation of primitive adipocytes, in which histological features can be ambiguous. In order to discriminate between lipoblastoma and other lipogenic and lipomatous tumours, we studied chromosomal alterations and protein expression in two cases of lipoblastoma in infants. Methods and results Standard cytogenetic analysis, fluorescence in-situ hybridization, array comparative genomic hybridization and Western blotting allowed us to demonstrate the presence of chromosome abnormalities involving the 8q11–13 region containing the pleomorphic adenoma gene 1 (PLAG1), which are classically reported in lipoblastoma, and aberrant expression of PLAG1. Conclusions This report illustrates two different tumorigenic pathways implicating PLAG1 in lipoblastoma: amplification through multiple copies of a small marker chromosome derived from chromosome 8, and a paracentric inversion of the long arm of chromosome 8. Both these anomalies induced aberrant expression of PLAG1, emphasizing the role of PLAG1 in tumorigenesis. The aberrant expression of PLAG1 protein has been hypothesized, but this is the first report to demonstrate its occurrence in lipoblastoma.