TGIF1

Researchers present abstracts and poster sessions showcasing research and clinical solutions Joint session planned with Illumina HOUSTON, March 04, 2024 (GLOBE NEWSWIRE) -- Baylor Genetics, a clinical diagnostic laboratory at the forefront of genetic testing, will showcase its latest advancements and research discoveries at the American College of Medical Genetics and Genomics (ACMG) Annual Clinical Genetics Meeting on March 12-16 in Toronto, Canada. The presentations shed light on cutting-edge developments in genetic analysis, diagnostic interpretation, and clinical results, underscoring Baylor Genetics’ mission to translate scientific innovation into accessible clinical solutions that improve patient outcomes and advance precision diagnostics. Exhibit Theater Presentation In a joint Exhibit Theatre Session, Christine Eng, M.D., Chief Medical Officer and Chief Quality Officer at Baylor Genetics, will speak about “Preparing for a Genome World | AI and Informatics Automation at the Core.” The session will take place in Exhibit Theater 2, presented by Illumina, Inc., on Thursday, March 14, from 11:55 a.m. to 12:25 p.m. (EST). Panel Presentation In a panel presentation titled, “Think Rare: Solving the Undiagnosed Cases Beyond Exome or Genome Sequencing,” Pengfei Liu, Ph.D., associate clinical director of research at Baylor Genetics, will participate on March 13 from 4:00 – 5:30 p.m. (EST) in Meeting Room 701. He will present on, “The Utility of Transcriptome RNA-Seq Analysis in Disease Diagnostics and Variant Interpretation,” from 4:30 – 4:45 p.m. (EST) and participate in the panel discussion to follow at 5:15 p.m. (EST). Poster Presentations March 14, 10:30 a.m. – 12:00 p.m. (EST) Detection of Single-Gene Copy Number Variations Through High-Resolution Exon-Targeted Chromosomal Microarray Analysis Primary Author: Dr. Matthew Hoi Kin Chau Novel Presentation of Dextrocardia in TGIF1 Holoprosencephaly Primary Author: Dr. Casey Thornton Pathogenic ZIC2 Polyalanine Expansion Detected by Exome Sequencing in a Family with Multi-Generation Holoprosencephaly Primary Author: Dr. Nichole Owen More Than an Extra Chromosome: Unexpected Multiple Diagnoses in Individuals with Down Syndrome Primary Author: Dr. Liesbeth Vossaert March 15, 10:30 a.m. - 12:00 p.m. (EST) Development of a Comprehensive Gene-/Disease-Specific Analysis and Knowledge Base to Enhance the Efficiency and Accuracy of Sequence Variant Interpretation and Clinical Reporting Primary Author: Dr. Xi Luo Phenotype Expansion or Multiple Diagnosis: Experience from Additional Findings in Patients with Common Aneuploidies Primary Author: Dr. Xiaonan Zhao Heterozygous Deletion of Valine at Position 2321 of RYR2 in Two Siblings with Sudden Cardiac Death Primary Author: Dr. Eric Kao Positive Findings in Clinical Mitochondrial Genome Testing by NGS Primary Author: Dr. Yue Wang PMP22 Single Exon Deletion in a Proband with Hematologic Malignancy and Family History of Charcot-Marie-Tooth Disease Primary Author: Dr. Katharina Schulze "The insights and research findings we share at ACMG 2024 spotlight the power of ongoing collaboration with leading industry partners, children’s hospitals, healthcare providers, academic and research organizations," said Kengo Takishima, President and Chief Executive Officer of Baylor Genetics. "These presentations reflect our ongoing commitment to advancing the field of genetics and empowering patients, providers, and partners with insights and innovations to transform healthcare and improve lives." Baylor Genetics invites attendees to visit its exhibit at Booth #1200, as well as attend presentations and poster session to learn more about research, offerings and advancements in whole genome and exome sequencing, reproductive health, critical care, oncology, disease-specific panels and complementary solutions. The company will host a networking breakfast on Thursday, March 14. Customers and partners interested in attending the breakfast can request an invitation and register here or inquire onsite at the Baylor Genetics booth. Learn more about ACMG’s Annual Clinical Genetics Meeting through the conference website and visit the Baylor Genetics’ website to explore the company’s genetic testing capabilities. About Baylor Genetics A pioneer of precision diagnostics for over 45 years, Baylor Genetics is a leading diagnostic genomics partner offering a full spectrum of clinically relevant genetic testing, including Whole Genome Sequencing, Whole Exome Sequencing, and focused panels. A joint venture of H.U. Group Holdings, Inc. and Baylor College of Medicine, which has the #1 NIH-funded Department of Molecular and Human Genetics, Baylor Genetics couples the fastest and most comprehensive precision diagnostics options with the support of genetic counselors to help clinicians and their patients avoid a lengthy diagnostic odyssey, guide medical management, and make sure no patient with a genetic disorder gets left behind. Its test menu spans from family planning, pregnancy, neonatal and pediatric testing, oncology, and specialized test options. Baylor Genetics is located in Houston’s Texas Medical Center and serves clients in 50 states and 16 countries.

导读：心脏纤维化在糖尿病心肌病（DCM）的进展中起着关键作用。之前的研究证明了利钠肽的心脏保护作用。然而，利钠肽受体 C (NPRC) 对 DCM 心脏纤维化的影响仍不清楚。近日，山东大学齐鲁医院研究人员在知名期刊《Science Advances》上发表了题为“NPRC deletion attenuates cardiac fibrosis in diabetic mice by activating PKA/PKG and inhibiting TGF-β1/Smad pathways”的研究论文。在该研究中，研究人员观察到心肌NPRC表达在小鼠和DCM患者中升高。NPRC在心脏成纤维细胞和心肌细胞中的敲除均降低了胶原合成和心脏成纤维细胞的增殖。RNA测序发现NPRC缺失上调TGF-β -诱导因子同源盒1 (TGIF1)的表达，抑制Smad2/3的磷酸化。此外，TGIF1上调是由NPRC缺失诱导的cAMP/PKA和cGMP/PKG信号激活介导的。这些发现表明，NPRC缺失减轻了糖尿病小鼠的心脏纤维化，改善了心脏重塑和功能，为治疗糖尿病性心脏纤维化提供了一种有希望的方法。https://www-science-org.libproxy1.nus.edu.sg/doi/full/10.1126/sciadv.add4222研究背景 01 糖尿病(DM)的患病率在过去十年中不断增加，给全球公共卫生造成了沉重的负担。流行病学研究，如弗雷明汉心脏研究，已经建立了糖尿病与心力衰竭(HF)风险增加之间的密切联系。糖尿病心肌病(DCM)，指的是一系列独立于糖尿病大血管并发症的心脏结构和功能异常。尽管对DCM进行了大量的研究，但有效的治疗方法很少，单独控制血糖往往不能改善心功能和预后。因此，进一步研究新的DCM治疗方法是非常必要的。DCM最初表现为舒张功能障碍，但逐渐发展为收缩功能障碍。DCM的发病机制是由代谢紊乱引发的，导致线粒体功能障碍、氧化应激和自噬受损。总之，这些影响可能导致心脏肥大、纤维化和炎症以及心肌细胞(CM)死亡，这不可避免地导致DCM。大量证据表明，糖尿病患者表现出明显的心肌纤维化，其特征是左右心室细胞外基质(ECM)的过度积累。目前，尚无循证疗法显示对糖尿病患者心脏纤维化的有益作用，这表明糖尿病心脏纤维化的机制有待进一步探索，以寻找新的治疗靶点。研究过程及发现 02 本研究有几个重要的发现。首先，NPRC 表达在糖尿病、心力衰竭患者和糖尿病小鼠的心脏以及经 HG 处理的 CF 中上调。其次，NPRC 缺失通过减轻体内心脏纤维化来改善左心室功能和重构。第三，NPRC 缺陷通过靶向 TGIF1 和 TGF-β1 抑制 TGF-β1/Smad 信号传导，从而减少体外 CF 中的胶原合成和增殖。最后，NPRC 缺失对心脏纤维化和 CF 的影响是通过激活 cAMP/PKA 和 cGMP/PKG 信号传导诱导的。据知，本研究是文献中第一个报告 NPRC 缺失对 DM 心脏纤维化的有益影响及其分子机制的研究。本研究证明了 NPRC 表达在糖尿病和心力衰竭患者以及糖尿病小鼠的心脏中上调。此外，CF中的NPRC表达高于CM中，并且高糖处理增强了NRCF和hiPSC-CF中的NPRC表达，表明NPRC参与了DCM的发病机制。为了探索 NPRC 在 DCM 中的调节作用，研究人员生成了 NPRC −/−小鼠，并通过在 NPRC −/−和同窝 WT 小鼠中注射 STZ 建立了糖尿病表型。与 WT 糖尿病小鼠相比，NPRC −/−小鼠的心脏重塑和功能得到改善。由于血糖水平没有观察到显着变化，NPRC 缺失可能通过直接靶向作用而不是通过血糖控制来保护小鼠免受 DCM。在与 DCM 相关的病理机制中，心脏纤维化导致心功能障碍和室性心律失常，导致预后不良。由于 CF 在心脏纤维化中发挥着关键作用，因此研究人员在本研究中重点关注 CF 与 DCM 之间的关系。小鼠系统性 NPRC 缺失的一个主要缺点是骨骼异常和收缩压降低。因此，在这里，研究人员使用携带 shNPRC 的 AAV9 来特异性敲低心肌中 NPRC 的表达。为了研究 NPRC 缺失对 DCM 发展影响的具体机制，研究人员重点关注 TGF-β1/Smad 信号传导，因为它在心脏纤维化中发挥着重要作用。研究结果揭示 NPRC 缺陷抑制 TGF-β1/Smad 信号传导的以下机制：NPRC 缺陷诱导 TGIF1 上调。研究人员进一步探讨了 NPRC 缺陷诱导 TGIF1 表达的详细机制。体外实验中，研究人员使用从大鼠中分离的NRCF和从小鼠中分离的MCF来探讨NPRC缺陷对CF的影响。为了进一步验证从动物细胞获得的实验结果，还使用了从 hiPSC 分化而来的 CF 和 CM，它们已越来越多地应用于心脏病建模和药物筛选。研究发现提供了对高葡萄糖刺激下人类 CF 和 CM 中 NPRC 相关信号传导的见解，并揭示了 DCM 心脏纤维化的有希望的治疗靶点。NPRC 缺陷对 DCM 心脏纤维化影响的潜在机制研究意义 03 总之，研究结果表明DCM 中 NPRC 表达增加，NPRC 缺乏可减轻心脏纤维化并改善心脏重塑和功能。因此，通过心脏特异性基因或药物治疗抑制 NPRC 为治疗糖尿病相关的心脏纤维化提供了一种有前景的方法。参考资料：https://www-science-org.libproxy1.nus.edu.sg/doi/full/10.1126/sciadv.add4222