Genetic Study in Left Ventricular Noncompaction

Background—Left ventricular noncompaction (LVNC) has since been classified as a primary genetic cardiomyopathy, but the genetic basis is not fully evaluated. The aim of the present study was to identify the genetic spectrum using next-generation sequencing and to evaluate genotype–phenotype correlations in LVNC patients. Methods and Results—Using next-generation sequencing, we targeted and sequenced 73 genes related to cardiomyopathy in 102 unrelated LVNC patients. We identified 43 pathogenic variants in 16 genes in 39 patients (38%); 28 were novel variants. Sarcomere gene variants accounted for 63%, and variants in genes associated with channelopathies accounted for 12%. MYH7 and TAZ pathogenic variants were the most common, and rare variant collapsing analysis showed variants in these genes contributed to the risk of LVNC, although patients carrying MYH7 and TAZ pathogenic variants displayed different phenotypes. Patients with pathogenic variants had early age of onset and more severely decreased left ventricular ejection fractions. Survival analysis showed poorer prognosis in patients with pathogenic variants, especially those with multiple variants: All died before their first birthdays. Adverse events were noted in 17 patients, including 13 deaths, 3 heart transplants, and 1 implantable cardioverter-defibrillator insertion. Congestive heart failure at diagnosis and pathogenic variants were independent risk factors for these adverse events. Conclusions—Next-generation sequencing revealed a wide spectrum of genetic variations and a high incidence of pathogenic variants in LVNC patients. These pathogenic variants were independent risk factors for adverse events. Patients harboring pathogenic variants showed poor prognosis and should be followed closely

List of all cell lines screened for 15 viruses from Screening for 15 pathogenic viruses in human cell lines registered at the JCRB Cell Bank: characterization of <i>in vitro</i> human cells by viral infection

Human cell lines have been used in a variety of research fields as an <i>in vitro</i> model. These cells are all derived from human tissue samples, thus there is a possibility of virus infection. Virus tests are routinely performed in clinical practice, but are limited in cell lines. In this study, we investigated 15 kinds of viruses in 844 human cell lines registered at the Japanese Collection of Research Bioresources (JCRB) Cell Bank. Our real-time PCR analysis revealed that six viruses, EBV, HTLV-1, HBV, B19 V, HHV-6 and HHV-7, were detected in 43 cell lines. Of them, 20 cell lines were transformed by intentional infection <i>in vitro</i> with EBV or by HTLV-1. Viruses in the other 23 cell lines and one EBV transformed cell line are derived from an <i>in vivo</i> infection, including five de novo identifications of EBV, B19V or HHV-7 carriers. Among them, 17 cell lines were established from patients diagnosed with virus-associated diseases. However, the other seven cell lines originated from <i>in vivo</i> cells unrelated to disease or cellular tropism. Our approach to screen for a set of 15 viruses in each cell line has worked efficiently to identify these rare cases. Virus tests in cell lines contribute not only to safety assessments but also to investigation of <i>in vivo</i> viral infection which can be a characteristic feature of cell lines

Primers used for viral DNA test by real-time PCR; Primers used for viral RNA test by real-time PCR; HIV-1/HIV-2 positive cell lines from Screening for 15 pathogenic viruses in human cell lines registered at the JCRB Cell Bank: characterization of <i>in vitro</i> human cells by viral infection

Human cell lines have been used in a variety of research fields as an <i>in vitro</i> model. These cells are all derived from human tissue samples, thus there is a possibility of virus infection. Virus tests are routinely performed in clinical practice, but are limited in cell lines. In this study, we investigated 15 kinds of viruses in 844 human cell lines registered at the Japanese Collection of Research Bioresources (JCRB) Cell Bank. Our real-time PCR analysis revealed that six viruses, EBV, HTLV-1, HBV, B19 V, HHV-6 and HHV-7, were detected in 43 cell lines. Of them, 20 cell lines were transformed by intentional infection <i>in vitro</i> with EBV or by HTLV-1. Viruses in the other 23 cell lines and one EBV transformed cell line are derived from an <i>in vivo</i> infection, including five de novo identifications of EBV, B19V or HHV-7 carriers. Among them, 17 cell lines were established from patients diagnosed with virus-associated diseases. However, the other seven cell lines originated from <i>in vivo</i> cells unrelated to disease or cellular tropism. Our approach to screen for a set of 15 viruses in each cell line has worked efficiently to identify these rare cases. Virus tests in cell lines contribute not only to safety assessments but also to investigation of <i>in vivo</i> viral infection which can be a characteristic feature of cell lines

Primers used for viral DNA test by real-time PCR; Primers used for viral RNA test by real-time PCR; HIV-1/HIV-2 positive cell lines from Screening for 15 pathogenic viruses in human cell lines registered at the JCRB Cell Bank: characterization of <i>in vitro</i> human cells by viral infection

Human cell lines have been used in a variety of research fields as an <i>in vitro</i> model. These cells are all derived from human tissue samples, thus there is a possibility of virus infection. Virus tests are routinely performed in clinical practice, but are limited in cell lines. In this study, we investigated 15 kinds of viruses in 844 human cell lines registered at the Japanese Collection of Research Bioresources (JCRB) Cell Bank. Our real-time PCR analysis revealed that six viruses, EBV, HTLV-1, HBV, B19 V, HHV-6 and HHV-7, were detected in 43 cell lines including five de novo identifications of EBV, B19 V or HHV-7 carriers. Of them, 20 cell lines were transformed by intentional infection <i>in vitro</i> with EBV or by HTLV-1. Viruses in the other 24 cell lines correspond to an <i>in vivo</i> infection. Of them, 17 cell lines were established from patients diagnosed with virus-associated diseases. However, the other seven cell lines originated from <i>in vivo</i> cells unrelated to disease or cellular tropism. Our approach to screen for a set of 15 viruses in each cell line has efficiently worked to identify these rare cases. Virus tests in cell lines contribute not only to safety assessments but also to investigation of <i>in vivo</i> viral infection which can be a characteristic feature of cell lines

List of all cell lines screened for 15 viruses from Screening for 15 pathogenic viruses in human cell lines registered at the JCRB Cell Bank: characterization of <i>in vitro</i> human cells by viral infection

Human cell lines have been used in a variety of research fields as an <i>in vitro</i> model. These cells are all derived from human tissue samples, thus there is a possibility of virus infection. Virus tests are routinely performed in clinical practice, but are limited in cell lines. In this study, we investigated 15 kinds of viruses in 844 human cell lines registered at the Japanese Collection of Research Bioresources (JCRB) Cell Bank. Our real-time PCR analysis revealed that six viruses, EBV, HTLV-1, HBV, B19 V, HHV-6 and HHV-7, were detected in 43 cell lines including five de novo identifications of EBV, B19 V or HHV-7 carriers. Of them, 20 cell lines were transformed by intentional infection <i>in vitro</i> with EBV or by HTLV-1. Viruses in the other 24 cell lines correspond to an <i>in vivo</i> infection. Of them, 17 cell lines were established from patients diagnosed with virus-associated diseases. However, the other seven cell lines originated from <i>in vivo</i> cells unrelated to disease or cellular tropism. Our approach to screen for a set of 15 viruses in each cell line has efficiently worked to identify these rare cases. Virus tests in cell lines contribute not only to safety assessments but also to investigation of <i>in vivo</i> viral infection which can be a characteristic feature of cell lines