共找到 20 条结果
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
暂无摘要（点击查看详情）
Almost 70 years ago, the World Health Organization (WHO) decided to propose a "Classification of Tumours". Since then, a systematic and extensive classification system for tumours has been continuously developed in successive editions and nowadays closely interlinks with coding systems for cancer registries like the International Classification of Diseases for Oncology (ICD-O). Whereas past editions had their focus on histopathological aspects of tumour classification in different organ systems and topologies, to which (somatic) genetic alterations increasingly contributed, the current fifth edition of the WHO Classification for the first time includes a separate "Blue Book" volume on "Genetic Tumour Syndromes". Along with chapters dedicated to tumour predisposition inferred by constitutional (germline) genetic pathogenic variants in the different organ-specific volumes of the classification, this new addition to the WHO classification highlights the increasing importance of constitutional genetic alterations for the diagnosis and clinical management of patients with such tumours. The WHO classification of Genetic Tumour Syndromes applies a hierarchical system based on four levels: the major (cellular) mechanism affected, the molecular pathway involved, the (clinical) syndrome, and the specific gene(s) affected. It provides - in part novel or modified - names to the genetic tumour syndromes as well as definitions and descriptions of clinical, epidemiologic, etiologic, pathogenetic and pathological aspects. Essential and desirable diagnostic criteria are given as well as rules for reporting, thus paving the way to international standardization. While the final version of the WHO Classification of Genetic Tumour Syndromes is in proof-stage, the present article, which is based on its beta-version, aims to provide an overview of the concepts underpinning the classification.
Chronic kidney disease (CKD) represents a significant global health burden, with diverse etiologies and often complex clinical presentations. Among these, a notable subset of CKD patients present without a clear underlying cause despite extensive diagnostic evaluation. For this subgroup, the term CKDx - chronic kidney disease of unexplained cause, has recently been proposed. A major element of the diagnostic workup of CKDx is genetic testing, for which the methodology has greatly improved in the last years.
Congenital anomalies of the kidney and urinary tract (CAKUT) represent a heterogeneous group of developmental disorders and are the leading cause of pediatric chronic kidney disease worldwide. The phenotypic spectrum is broad, encompassing kidney agenesis, hypodysplasia, multicystic dysplastic kidneys, vesicoureteral reflux, obstructive uropathies, and other malformations affecting the kidneys, ureters, and urethra. Advances in genetics have begun to unravel the molecular pathways underlying these diverse phenotypes, yet the complexity of CAKUT reflects contributions from both monogenic variants and multifactorial causes. This review provides an overview of the current understanding of the genetic causes of CAKUT, beginning with fundamental principles of kidney and urinary tract development, and then focusing on major discoveries in the past ten years. We aim to summarize key genetic findings, with an emphasis on genotype-phenotype correlations and developmental pathways, highlight emerging mechanisms, and discuss their implications for diagnosis, counseling, and clinical management.
Antisense oligonucleotides (ASOs) are a promising therapeutic modality for monogenic disorders, offering precise RNA-targeting strategies to modulate gene expression. Despite challenges in delivery, toxicity, and off-target effects, ASO therapies have advanced rapidly, with several approved treatments and numerous candidates in clinical development. Their application spans neurogenetic, metabolic, and oncologic disorders, also with emerging n-of-1 approaches for ultra-rare conditions. This review describes the different mechanism of how ASOs work depending on their chemistry and discusses the considerations of which patients could be amendable for treatment highlighting the role of human genetics for decision making.
For a long time, a comprehensive postmortem examination has been the most important investigation in unexplained fetal and neonatal deaths. In recent years, the usefulness of autopsy has been questioned due to the availability of improved prenatal imaging techniques and genome-wide sequencing that allow an early prenatal diagnosis of an increasing number of disorders. While concordance rates of prenatal ultrasound and postmortem findings are high, fetal autopsy may provide additional information in many cases and allow more accurate counseling of parents regarding the recurrence risk and management in future pregnancies. In this article, we provide a brief outline of a systematic fetal and placental evaluation by pathology and clinical genetics. Based on selected cases, the advantages of a comprehensive postmortem evaluation will be illustrated with emphasis on its role in quality control of prenatal ultrasound after termination of pregnancy, comprehensive and deep phenotyping, the interpretation of genetic variants and its high educational value.