Triple repeated fetal congenital heart disease linked to PLD1 mutation: a case report

Abstract Background Congenital heart disease occurs in approximately 1 in 100 cases. Although sibling occurrence is high (3–9%), the causative genes for this disease are still being elucidated. PLD1 (Phospholipase D1) is a recently discovered gene; however, few case reports have been published on it. In this report, we describe a case of triplicate fetal congenital heart disease that was diagnosed as a PDL1 mutation. Our objective is to explore the clinical manifestations of PLD1 mutations in this particular case. Case presentation A 32-year-old Japanese woman (gravida, para 0) was introduced since fetus four chamber view was not clear and was diagnosed with ductus arteriosus-dependent left ventricular single ventricle and pulmonary atresia at 21 weeks and 1 day of gestation during her first pregnancy. Artificial abortion using Gemeprost was performed at 21 weeks and 5 days of gestation. The second pregnancy was diagnosed as pulmonary atresia with intact ventricular septum with cardiomegaly, a cardiothoracic area ratio of more than 35%, and a circulatory shunt at 13 weeks and 3 days of gestation. Subsequently, intrauterine fetal death was confirmed at 14 weeks and 3 days of gestation. Regarding the third pregnancy, fetal ultrasonography at 11 weeks and 5 days of gestation showed mild fetal hydrops and moderate tricuspid valve regurgitation. At 16 weeks and 5 days of gestation, the fetus was suspected to have a left ventricular-type single ventricle, trace right ventricle, pulmonary atresia with intact ventricular septum, or cardiomyopathy. Cardiac function gradually declined at 26 weeks of gestation, and intrauterine fetal death was confirmed at 27 weeks and 5 days of gestation. The fourth pregnancy resulted in a normal heart with good progression and no abnormal baby. We submitted the first and second fetuses’ umbilical cord, third fetus’ placenta, and the fourth fetus’ blood to genetic testing using whole exome analysis with next generation sequencing. Genetic analysis identified hemizygous PLD1 mutations in the first, second, and third fetuses. The fourth fetus was heterozygous. In addition, the parents were heterozygous for PLD1. This case is based on three consecutive cases of homozygosity for the PLD1 gene in the sibling cases and the fetuses with recurrent right ventricular valve dysplasia. This will elucidate the cause of recurrent congenital heart disease and intrauterine fetal death and may serve as an indicator for screening the next fetus. To date, homozygous mutations in PLD1 that repeat three times in a row are not reported, only up to two times. The novelty of this report is that it was repeated three times, followed by a heterozygous live birth. Conclusions This report is consistent with previous reports that mutations in PLD1 cause right ventricular valve dysplasia. However, there have been few case reports of PLD1 mutations, and we hope that this report will contribute to elucidate the causes of congenital heart disease, especially right ventricular valve dysplasia, and that the accumulation of such information will provide more detailed information on PLD1 mutations in heart disease

Cancer-Specific miRNAs Extracted from Tissue-Exudative Extracellular Vesicles in Ovarian Clear Cell Carcinoma

Ovarian clear cell carcinomas (OCCs) arise from endometriotic cysts that many women develop. Biomarkers for early OCC detection need to be identified. Extracellular vesicles have attracted attention as biomarker carriers. This study aims to identify cancer-specific miRNAs as novel OCC biomarkers using tissue-exudative extracellular vesicles (Te-EVs). Te-EVs were collected from four patients with OCC on one side and a normal ovary on the other side. Microarray analysis was performed to identify cancer-specific miRNAs in Te-EVs. Serum samples obtained before and after surgery from patients with OCC and atypical endometrial hyperplasia (AEH) (controls) were compared using real-time PCR to examine changes in the detected EV miRNA levels. Thirty-seven miRNAs were >2-fold upregulated on the OCC side compared with the normal ovarian side. We selected 17 miRNAs and created specific primers for 12 of these miRNAs. The levels of six EV miRNAs were significantly decreased in postoperative OCC serum compared to those in preoperative OCC serum. In contrast, no significant change was observed between the pre and postoperative values in the control group. We identified OCC tissue-specific miRNAs in the EVs secreted by OCC tissues. These EV miRNAs have potential for use as biomarkers for the early diagnosis and detection of OCC

Structural and Electrochemical Characterization of Ethylenediaminated Single-Walled Carbon Nanotubes Prepared from Fluorinated SWCNTs

We prepared ethylenediaminated single-walled carbon nanotubes (SWCNTs) from fluorinated SWCNTs by substituting fluorine groups with ethylenediamine groups. The ethylenediaminated SWCNTs were characterized by scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), Raman scattering spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, Brunauer–Emmett–Teller surface area measurement by nitrogen adsorption, contact angle measurement, zeta potential analysis, and thermogravimetry. In addition, the properties of 30 wt % sulfuric acid aqueous electrolyte-based electric double-layer supercapacitors (EDLSCs) with free-standing ethylenediaminated SWCNT electrodes were investigated. The degree of ethylenediamine functionalization was 0.603 mmol/g and 1.46 μmol/m², and the specific surface area was ∼413.3 m²/g. From HRTEM observation, isolated nanotubes disentangled from the bundled SWCNTs were present in many observed areas, and the structures retained a nanotube skeleton. The properties of the EDLSCs with the ethylenediaminated SWCNT electrodes included an average specific capacitance of 94 F/g at a low scan rate of 10 mV/s and an energy density of 2.6 Wh/kg at a power density of 0.24 kW/kg. The EDLSCs exhibited an average specific capacitance of 67 F/g at a high scan rate of 1000 mV/s and an energy density of 1.3 Wh/kg at a power density of 24 kW/kg, values that were superior to those of carboxylated SWCNT electrodes