Beta myosin heavy chain mutations R403QLW, V606M, K615N and R663H in patients with hypertrophic cardiomyopathy

Abstract

Objective: Hypertrophic cardiomyopathy (HCM) is a disease of the myocardium with an autosomal-dominant pattern of inheritance mainly caused by single heterozygous mutations in sarcomere genes. In this study we aimed to detect the presence of R403QLW, V606M, K615N, and R663H mutations in beta-myosin heavy-chain gene (MYH7) and figure out the genotype-phenotype correlations in Turkish patients with HCM. Methods: This case-control study based on genotype-phenotype correlation included 69 patients (mean age, years: 50±13.16) diagnosed with HCM constituting the study group and 50 healthy individuals (mean age, years: 52±1.4) constituting the control group. DNA was extracted from peripheral blood and the genotyping of mutations was performed by real-time PCR technique and high resolution melting analysis. Associations between categoric variables were determined using chi-square tests. Differences between two groups were compared with unpaired Student's t-test for continuous variables. Results: None of the patients in the HCM group were carrying the index mutations. One healthy individual was found to be heterozygous for the R663H mutation with mildly abnormal IVS and LVPW thickness. The allele frequency for R663H (G>A) mutation was found to be 0.01% in control group. Conclusion: We performed a mutational screening of 6 HCM-associated mutations in 69 Turkish HCM patients (not previously studied except R403Q). There was no significant difference in the prevalence of the mutations between the patients with HCM and the healthy controls (p>0.05). (Anadolu Kardiyol Derg 2014; 14: 244-50)

Insights into the Proteome of Gastrointestinal Stromal Tumors-Derived Exosomes Reveals New Potential Diagnostic Biomarkers

“…Intercellular communication is crucial to maintain homeostasis or, in certain instances, promote tumorigenesis (1,2). As shown by our group and others, exosomes create environments that are favorable to tumor progression, invasion, angiogenesis, metastasis, and drug response (31,70,71). Exosomes are present and readily accessible in many bodily fluids, including blood, saliva, urine, cerebrospinal, and ascites fluids (72)(73)(74).…”

“…Therefore, there is an urgent need for additional therapeutic strategies and/or discovery of therapeutic markers that will significantly enhance follow-up and predict response to therapy for these tumors. One possible source of biomarkers, as reported by us ad others, is the presence in the systemic circulation of GIST patients of modulatory KIT positive nanovesicles (31).…”

“…The KIT mutation status of the cell lines was confirmed using the TruSeq Amplicon -Cancer Panel (TSACP) from Illumina. These cells have been extensively characterized previously and are representative of the behavior, genotype, and phenotype of GIST (31). The cells were maintained in Dulbecco's modified Eagle's medium (Gibco Invitrogen) supplemented with 100 units/ml penicillin-streptomycin and 10% exosomes-depleted FBS and maintained at 37°C with 5% CO 2 .…”

“…GIST882 and GIST-T1 cells possess a K642E mutation in exon 13 of KIT or a 57nucleotide (V570-Y578) in-frame deletion in exon 11 of KIT, respectively. A nontransformed primary myometrial smooth muscle cells (1°SMC), which represent the host cells surrounding these tumors in vivo was included as a control (31). As shown in Fig.…”

“…Our previous studies have shown that gastrointestinal stromal tumors (GISTs) release "oncosomes" carrying the oncogenic tyrosine kinase receptor (RTK) c-KIT, which is important for GIST invasion and disease progression (27,31). GIST is a rare but deadly mesenchymal malignancy affecting the gastrointestinal tract (GI) (32,33).…”