Mitochondria play a fundamental role during development of the female germline. They are fragmented, round, and small. Despite these characteristics suggesting that they are inactive, there is accumulating evidence that mitochondrial dysfunctions are a major cause of infertility and generation of aneuploidies in humans. In addition, mitochondria and their own genomes (mitochondrial DNA-mtDNA) may become damaged with time, which might be one reason why aging leads to infertility. As a result, mitochondria have been proposed as an important target for evaluating oocyte and embryo quality, and developing treatments for female infertility. On the other hand, mutations in mtDNA may cause mitochondrial dysfunctions, leading to severe diseases that affect 1 in 4,300 people. Moreover, very low levels of mutated mtDNA seem to be present in every person worldwide. These may increase with time and associate with late-onset degenerative diseases such as Parkinson disease, Alzheimer disease, and common cancers. Mutations in mtDNA are transmitted down the maternal lineage, following a poorly understood pattern of inheritance. Recent findings have indicated existence in the female germline of a purifying filter against deleterious mtDNA variants. Although the underlying mechanism of this filter is largely unknown, it has been suggested to rely on autophagic degradation of dysfunctional mitochondria or selective replication/transmission of non-deleterious variants. Thus, understanding the mechanisms regulating mitochondrial inheritance is important both to improve diagnosis and develop therapeutic tools for preventing transmission of mtDNA-encoded diseases.
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http://dx.doi.org/10.1002/cbin.10947 | DOI Listing |
Calcif Tissue Int
January 2025
Department of Endocrinology, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium.
Hyperparathyroidism-jaw tumor syndrome is a rare form of syndromic primary hyperparathyroidism. We describe a young female with a history of common precursor B acute lymphoblastic leukaemia who was diagnosed with overt primary hyperparathyroidism due to a pathogenic CDC73 variant (c.25C > T).
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Background: Fundamental questions remain about the key mechanisms that initiate Alzheimer's disease (AD) and the factors that promote its progression. Here we report the successful generation of the first genetically-engineered marmosets that carry knock-in (KI) point mutations in the presenilin-1 (PSEN1) gene that can be studied from birth throughout lifespan.
Method: CRISPR/Cas9 was used to generate marmosets with C410Y or A426P point mutations in PSEN1.
Cancer
January 2025
Division of Clinical Cancer Genomics, Department of Medical Oncology, City of Hope National Medical Center, Duarte, California, USA.
Background: The authors assessed the feasibility, acceptability, and impact on cancer worry of a cancer screening program using multicancer early detection (MCED) tests and whole-body magnetic resonance imaging (WBM) in individuals at high cancer risk because of family history or germline variants in cancer-susceptibility genes.
Methods: This prospective trial enrolled participants aged 50 years and older who had a significant family history of cancer or a cancer-susceptibility gene variant. Participants underwent noncontrast WBM and MCED testing.
Science
January 2025
Cancer Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Pediatric solid tumors are a leading cause of childhood disease mortality. In this work, we examined germline structural variants (SVs) as risk factors for pediatric extracranial solid tumors using germline genome sequencing of 1765 affected children, their 943 unaffected parents, and 6665 adult controls. We discovered a sex-biased association between very large (>1 megabase) germline chromosomal abnormalities and increased risk of solid tumors in male children.
View Article and Find Full Text PDFActa Gastroenterol Belg
January 2025
Department of Gastroenterology, UZ Ghent, Ghent, Belgium.
Background: Pancreatic ductal adenocarcinoma (PDAC) has a known poor prognosis. For a select group, those with BRCA mutations, frontline platinum-based therapy and poly (ADPribose) polymerase inhibitors are options that can potentially lead to survival benefit.
Patients And Methods: We present 2 cases of patients with BRCAmutated pancreatic cancer with liver metastases that achieved a remarkable long-term complete remission on platinum-based chemotherapy.
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