We describe a young woman with a mosaic form of neurofibromatosis type 1 (MNF1). In mosaicism, a genetic change occurs after conception and is therefore present in only some cells of the body rather than all cells. As a result, standard blood tests may miss the genetic change, especially in people who only have limited […]
Latest articles
Updated ENIGMA recommendations for reporting germline variants in cancer susceptibility genes and their translation into twenty languages (Contributed by Prof. Arcangela De Nicolo)
Genetic testing for cancer predisposition informs precision cancer prevention and care. Clear understanding and communication of the cancer risk associated with each identified gene variant underlies responsible decision-making. We describe an initiative promoted by the ENIGMA consortium that involved 70 scientists from 25 countries worldwide to harmonize reporting of germline genetic test results for breast […]
Biallelic variants in DNAH10 are associated with skeletalf developmental abnormalities and ciliary dysfunction (Contributed by Rui Zheng)
Primary cilia are tiny hair-like structures on many cells that act as antennae, helping cells receive signals needed for normal development. In this study, we identified DNAH10 variants in two children with skeletal abnormalities, including thumb defects and changes in the ribs or spine. Using cell experiments and a mouse model, we found that loss […]
Best practice recommendations for bioinformatics approaches applied to high-throughput sequencing for rare disease and cancer diagnosis within the UK National Health Service
A new UK NHS bioinformatics framework provides updated best-practice recommendations for high-throughput sequencing in rare disease and cancer diagnosis. Addressing the full diagnostic pipeline, from data quality to interpretation and knowledge sharing, it provides a practical foundation for more consistent and equitable clinical genomics. It aligns bioinformatics practice with the growing scale and complexity of […]
Long-read genome sequencing increases diagnostic yield in a short-read sequencing unsolved developmental epileptic encephalopathy (DEE) cohort (Contributed by Chanatjit Cheawsamoot)
Severe childhood epilepsies with developmental delay, known as developmental and epileptic encephalopathies (DEE), are often caused by genetic changes. However, standard DNA tests, such as exome sequencing and short-read genome sequencing, sometimes fail to identify the underlying genetic cause. In this study, we used long-read genome sequencing (LR-GS) to analyze patients with DEE who remained […]
Damaging missense variants in innate immunity genes are associated with earlier age of breast cancer onset in BRCA1 185delAG carriers (Contributed by Prof. Rani Elkon)
BRCA1 is the major risk gene for breast cancer. However, not all women who carry harmful BRCA1 mutations (‘BRCA1 carriers’) develop breast cancer, and those who do can be diagnosed at very different ages, suggesting that additional factors influence the risk of BRCA1 carriers. This study analyzed the protein-coding genes of 321 Israeli women who […]
VHL gene fragment analysis: large inversion detection in Alu region for clinical applications (Contributed by Ryan Baugher)
Von Hippel-Lindau (VHL) syndrome is a disorder that puts patients at increased risk of developing benign and malignant tumors within various organs. While current genetic tests demonstrate successful detection of minor mutations, large structural rearrangements of the genome are undetectable by existing tests, indicating need for custom test to confirm these large alterations. We validated […]
Field Watch: FDA’s genome-editing guidance
The FDA’s new draft guidance on safety assessment for human genome-editing therapies reflects increasing regulatory attention to off-target edits, chromosomal alterations, and sequencing-based approaches to safety evaluation. It gives a sense of the questions likely to shape the next stage of clinical development, particularly how unintended genomic effects are detected, interpreted, and weighed. As genome […]
Optical Genome Mapping Identifies Previously Undetected Causal Variants in Early-Onset Developmental Epileptic Encephalopathies (Contributed by Sanem Yilmaz)
Developmental epileptic encephalopathies (DEEs) are severe childhood conditions that cause early-onset seizures and developmental delay. Although genetic testing can identify a cause in many patients, some remain undiagnosed despite extensive investigations. In this study, we used a newer method called optical genome mapping (OGM), which can detect certain genetic changes missed by standard tests. Among […]
Clinical Characteristics and Prognosis of SDHD Pathogenic Variant Carriers: A Systematic Review and Meta-Analysis (Contributed by Professor Bo Shen)
Individuals with an inherited pathogenic variant in the SDHD gene are at risk of developing rare tumours known as PPGLs. Our study synthesized global research to clarify how this cancer risk evolves across a patient’s lifetime. We found that the likelihood of developing a tumour rises significantly with age, reaching 82% by the age of […]