Triple mosaic variants of PURA in a patient with multiple congenital anomalies.

In monogenic diseases, double mosaic variants of the same gene have rarely been identified. Here, we report the case of triple mosaic variants in PURA, a gene responsible for a neurodevelopmental syndrome (OMIM# 616158). Whole-exome sequencing identified three somatic PURA variants in our case with a similar neurodevelopmental syndrome: NM_005859.

Long-term clinical course of adult-onset refractory epilepsy in cardiofaciocutaneous syndrome with a pathogenic variant: a case report.

Cardiofaciocutaneous syndrome (CFC) is a rare genetic disorder that presents with cardiac, craniofacial, and cutaneous symptoms, and is often accompanied by neurological abnormalities, including neurodevelopmental disorders and epilepsy. Regarding epilepsy in CFC, the onset of seizures commonly occurs in childhood. Since research data has mainly been collected from young patients with relatively short observation period, there is insufficient information regarding adult-onset epilepsy in CFC.

Complex chromosomal 6q rearrangements revealed by combined long-molecule genomics technologies.

Technologies for detecting structural variation (SV) have advanced with the advent of long-read sequencing, which enables the validation of SV at a nucleotide level. Optical genome mapping (OGM), a technology based on physical mapping, can also provide comprehensive SVs analysis. We applied long-read whole genome sequencing (LRWGS) to accurately reconstruct breakpoint (BP) segments in a patient with complex chromosome 6q rearrangements that remained elusive by conventional karyotyping.

Long-read sequencing revealing intragenic deletions in exome-negative spastic paraplegias.

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and weakness in the lower extremities. To date, a total of 88 types of SPG are known. To diagnose HSP, multiple technologies, including microarray, direct sequencing, multiplex ligation-dependent probe amplification, and short-read next-generation sequencing, are often chosen based on the frequency of HSP subtypes.

Biallelic structural variations within detected by long-read sequencing in epilepsy.

We discovered biallelic intragenic structural variations (SVs) in by applying long-read whole genome sequencing to an exome-negative patient with developmental and epileptic encephalopathy (DEE). We also found another DEE patient carrying a biallelic (homozygous) single-nucleotide variant (SNV) in that was detected by exome sequencing. heterozygous recurrent missense variants with gain-of-function or heterozygous entire duplication of are known causes of epilepsy, but biallelic SNVs/SVs have never been described.

Brain monoamine vesicular transport disease caused by homozygous SLC18A2 variants: A study in 42 affected individuals.

Purpose: Brain monoamine vesicular transport disease is an infantile-onset movement disorder that mimics cerebral palsy. In 2013, the homozygous SLC18A2 variant, p.Pro387Leu, was first reported as a cause of this rare disorder, and dopamine agonists were efficient for treating affected individuals from a single large family.

Quantitative Myocardial Perfusion in Surgically Repaired Coronary Artery Anomaly.

The anomalous aortic origin of the right coronary artery with an intramural course is rare and can cause myocardial ischemia, for which surgical repair is indicated. We present the case of a 49-year-old man with this anomaly whose preoperative myocardial perfusion positron emission tomography revealed inducible ischemia. Comparison of the preoperative and follow-up (6 months) positron emission tomography findings showed significant improvement in regional myocardial flow reserve and relative flow reserve, in keeping with the improvement in symptoms.

Trifecta versus Perimount Magna Ease aortic valves: Failure mechanisms.

Background: There are increasing reports of early externally mounted pericardial Trifecta bioprosthesis failure. We compared the hemodynamic performance of Trifecta and Carpentier-Edwards Perimount Magna Ease valves to determine the failure mechanism.

Methods: We retrospectively included 270 consecutive patients (age: 73.

Large-scale discovery of novel neurodevelopmental disorder-related genes through a unified analysis of single-nucleotide and copy number variants.

Background: Previous large-scale studies of de novo variants identified a number of genes associated with neurodevelopmental disorders (NDDs); however, it was also predicted that many NDD-associated genes await discovery. Such genes can be discovered by integrating copy number variants (CNVs), which have not been fully considered in previous studies, and increasing the sample size.

Methods: We first constructed a model estimating the rates of de novo CNVs per gene from several factors such as gene length and number of exons.

Transcatheter aortic valve replacement failure: a case report of the bicuspid aortic valve type 0 with a single coronary artery.

Transcatheter aortic valve replacement (TAVR) is the treatment of choice for aortic stenosis. However, its safety and efficacy in patients with the bicuspid aortic valve (BAV) remain controversial. Especially, whether the BAV phenotype affects outcomes following TAVR remains debated.

Overexpression of PD-1 on T cells promotes tolerance in cardiac transplantation via ICOS-dependent mechanisms.

The programmed death 1/programmed death ligand 1 (PD-1/PD-L1) pathway is a potent inhibitory pathway involved in immune regulation and is a potential therapeutic target in transplantation. In this study, we show that overexpression of PD-1 on T cells (PD-1 Tg) promotes allograft tolerance in a fully MHC-mismatched cardiac transplant model when combined with costimulation blockade with CTLA-4-Ig. PD-1 overexpression on T cells also protected against chronic rejection in a single MHC II-mismatched cardiac transplant model, whereas the overexpression still allowed the generation of an effective immune response against an influenza A virus.

[Resection of a Myxoma Orginating from the Coumadin Ridge with Superior Transseptal Approach:Report of a Case].

A 70-year-old man with a history of lacunar stroke about a year before was incidentally found to have primary cardiac tumor during the work up for orthopedic surgery. It uniquely originated from the coumadin ridge between the left upper pulmonary vein and the left atrial appendage. He underwent tumor resection under cardiopulmonary bypass with superior transseptal approach.

Antiatherosclerotic Phenotype of Perivascular Adipose Tissue Surrounding the Saphenous Vein in Coronary Artery Bypass Grafting.

Background Perivascular adipose tissue (PVAT) is associated with metabolically driven chronic inflammation called metaflammation, which contributes to vascular function and the pathogenesis of vascular disease. The saphenous vein (SV) is commonly used as an essential conduit in coronary artery bypass grafting, but the long-term patency of SV grafts is a crucial issue. The use of the novel "no-touch" technique of SV harvesting together with its surrounding tissue has been reported to result in good long‑term graft patency of SV grafts.

Long-read whole-genome sequencing identified a partial MBD5 deletion in an exome-negative patient with neurodevelopmental disorder.

Whole-exome sequencing (WES) can detect not only single-nucleotide variants in causal genes, but also pathogenic copy-number variations using several methods. However, there may be overlooked pathogenic variations in the out of target genome regions of WES analysis (e.g.

A pipeline for complete characterization of complex germline rearrangements from long DNA reads.

Background: Many genetic/genomic disorders are caused by genomic rearrangements. Standard methods can often characterize these variations only partly, e.g.

[Early Clinical Outcomes of Robotic Mitral Valve Repair;Initial Twenty Cases].

We report the early results of our initial 20 consecutive robotic-assisted mitral valve repairs at our institution. A total of 20 patients (aged 55±10 years, 15 males) underwent robotic assisted mitral repairs by using da Vinci system. Successful mitral valve repairs were done in all cases.

A novel PAK1 variant causative of neurodevelopmental disorder with postnatal macrocephaly.

p21-activated kinases (PAKs) are protein serine/threonine kinases stimulated by Rho-family p21 GTPases such as CDC42 and RAC. PAKs have been implicated in several human disorders, with pathogenic variants in PAK3 associated with intellectual disability and several PAK members, especially PAK1 and PAK4, overexpressed in human cancer. Recently, de novo PAK1 variants were reported to be causative of neurodevelopmental disorder (ND) with secondary macrocephaly in three patients.

Magnetic Elastomers with Smart Variable Elasticity Mimetic to Sea Cucumber.

A magnetic-responsive elastomer consisting of magnetic elastomer and zinc oxide with a tetrapod shape and long arms was fabricated mimetic to the tissue of sea cucumber in which collagen fibrils are dispersed. Only the part of magnetic elastomer is active to magnetic fields, zinc oxide plays a role of reinforcement for the chain structure of magnetic particles formed under magnetic fields. The magnetic response of storage modulus for bimodal magnetic elastomers was measured when the magnetic particle was substituted to a nonmagnetic one, while keeping the total volume fraction of both particles.

Notch-1 Inhibition Promotes Immune Regulation in Transplantation Via Regulatory T Cell-Dependent Mechanisms.

Background: Transplantation is the treatment of choice for many patients with end-stage organ disease. Despite advances in immunosuppression, long-term outcomes remain suboptimal, hampered by drug toxicity and immune-mediated injury, the leading cause of late graft loss. The development of therapies that promote regulation while suppressing effector immunity is imperative to improve graft survival and minimize conventional immunosuppression.

[Surgical Treatment of Acute Infective Endocarditis after Transcatheter Aortic Valve Replacement].

Infective endocarditis (IE) after transcatheter aortic valve replacement (TAVR) is a rare complication, but has a high mortality. An 86-year-old female with symptomatic severe aortic stenosis underwent TAVR at our hospital and she was discharged without complication after 10 days. She was readmitted with high fever and acute heart failure 1 month later.

Ischemia augments alloimmune injury through IL-6-driven CD4 alloreactivity.

Ischemia reperfusion injuries (IRI) are unavoidable in solid organ transplantation. IRI augments alloimmunity but the mechanisms involved are poorly understood. Herein, we examined the effect of IRI on antigen specific alloimmunity.

Regulation of T cell alloimmunity by PI3Kγ and PI3Kδ.

Phosphatidylinositol-3-kinases (PI3K) γ and δ are preferentially enriched in leukocytes, and defects in these signaling pathways have been shown to impair T cell activation. The effects of PI3Kγ and PI3Kδ on alloimmunity remain underexplored. Here, we show that both PI3Kγ and PI3Kδ mice receiving heart allografts have suppression of alloreactive T effector cells and delayed acute rejection.

Testing the Efficacy of Contrast-Enhanced Ultrasound in Detecting Transplant Rejection Using a Murine Model of Heart Transplantation.

One of the key unmet needs to improve long-term outcomes of heart transplantation is to develop accurate, noninvasive, and practical diagnostic tools to detect transplant rejection. Early intragraft inflammation and endothelial cell injuries occur prior to advanced transplant rejection. We developed a novel diagnostic imaging platform to detect early declines in microvascular perfusion (MP) of cardiac transplants using contrast-enhanced ultrasonography (CEUS).