A study published in Science presents a single-cell atlas of DNA methylation and three-dimensional genome organization across the human body. Zhou and colleagues profiled 86,689 nuclei from 16 adult tissues, characterizing 35 major cell types and 206 subtypes. Their findings reveal extensive cell type–specific differences in methylation, chromatin loops, and long-range genome organization, while showing […]
Latest articles
Potential advantage of clinical exome sequencing in BRCA1/2-negative families: a retrospective study of a cohort of 500 patients at a high-risk for hereditary cancers (Contributed by Dr. Federico Anaclerio)
Many families with a strong history of cancer remain without a genetic diagnosis after standard BRCA1/2 testing. In this study, we investigated whether Clinical Exome Sequencing (CES) could provide additional genomic information in 500 high-risk individuals who previously tested negative for BRCA1/2 pathogenic variants. While most additional findings are not yet ready for routine clinical […]
Cancer Variant Interpretation Group UK (CanVIG-UK): updates on an exemplar national subspecialty multidisciplinary network (Contributed by Dr. Alice Garrett and Sophie Allen)
Cancer Variant Interpretation Group UK (CanVIG-UK) was established in 2017. Its initial purpose was to improve consistency in the interpretation of genetic data from cancer susceptibility genes (CSGs) in the NHS laboratories across the UK. Still convening for monthly national meetings, CanVIG-UK develops national consensus guidance and delivers training and education, among other key activities. […]
Frequent FBN2 Variants in Pectus Excavatum Highlight Underlying Phenotypic Variability (Contributed by Dr. Yongjia Yang)
Pectus excavatum (PE) is the most common chest wall deformity, causing a sunken breastbone that can affect breathing and heart function. Most cases occur without a known cause. In our study of 290 children with PE, we discovered that changes in the FBN2 gene—previously linked to a rare syndrome—are surprisingly common among these patients. Using […]
Longest surviving patient with a homozygous splice-altering EGFR pathogenic variant presenting with skin autoinflammation and a Bartter-like salt-losing tubulopathy (Contributed by Dr. Hassan Vahidnezhad)
Bartter syndrome is a rare inherited kidney disease that makes the body lose too much salt. Usually, the cause is a fault in one of seven known genes. None of this was observed in a teenage boy from an inbred family. Instead, his DNA had a change in a different gene, EGFR, which also affected […]
Functional Characterization and Pathological Significance of Variants of MEF2C Promoter in Tetralogy of Fallot (Contributed by Professor Guo-Wei HE)
Congenital heart disease (CHD) is the most common birth defect. Tetralogy of Fallot (TOF) is a severe form of CHD. While genetic changes in protein-coding regions are known to cause some cases, the role of non-coding regulatory regions remains unclear. Our study focused on the MEF2C promoter, which acts like a switch that controls gene […]
Concept watch: toward a “one-test” genome in medical genetics
Sabbagh and colleagues frame “near-perfect genome sequencing” as the convergence of long-read sequencing, diploid genome assembly, pangenome references and AI-assisted interpretation. The goal is to replace today’s fragmented diagnostic cascade and close short-read blind spots, including repeats, segmental duplications, complex structural variants, methylation and phasing. They propose that genomic completeness itself should inform variant classification, […]
INHERITED RETINAL DISEASE GENES WITH DUAL INHERITANCE PATTERNS: INSIGHTS FROM THE IRD-PT REGISTRY (Contributed by Mariana Francisco)
Inherited retinal diseases cause progressive vision loss and usually follow a single inheritance pattern, either dominant (one altered gene copy) or recessive (two altered copies). However, some “dual-inheritance” genes can cause disease through both modes, posing unique challenges for genetic counselling. Analysing data from Portugal’s national registry of over 1,100 patients, we identified nine such […]
PRS-BC313 integration for tailored breast cancer prevention in female patients and their healthy relatives (Contributed by Dr. Rosanna Krakowsky)
Women with a family history of hereditary breast cancer need precise risk estimates to guide screening decisions. We studied whether adding a polygenic risk score (PRS-BC313), capturing the combined effect of hundreds of common genetic variants, to standard risk calculations meaningfully changes individual breast cancer risk predictions. Among women without a known high-risk gene variant […]
Identification of Lynch syndrome among people newly diagnosed with endometrial cancer: a prospective audit (Contributed by Prof. Emma J Davidson)
The UK National Institute for Health and Care Excellence (NICE) recommends the unselected testing of all endometrial cancer patients for Lynch syndrome. This study found that while nearly all endometrial cancer patients discussed at a Gynaecological Cancer MDT in the North West of England were successfully screened for Lynch syndrome, not all high-risk individuals completed […]