In a recent report published in the New England Journal of Medicine, Gupta, Sharma, Frangoul, Kanter, Mapara, Dalal, Alavi, and colleagues described interim results from the phase 1–2 BEACON study evaluating ristoglogene autogetemcel (risto-cel) in patients with sickle cell disease. This base-editing approach targets the HBG1 and HBG2 promoters to increase fetal hemoglobin production while […]
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Expanded carrier screening in a Southwestern Chinese population indicates East Asian specific low-frequency pathogenic variants account for nearly half of the at-risk couple rate (Contributed by Sha Liu)
A study of over 3,700 people in China found that carrying hidden gene variants is common. Certain variants found mainly in East Asians significantly influence the chance that both partners carry the same condition. Screening based only on global data may miss these variants. Incorporating population-specific information can therefore provide a clearer picture for genetic […]
Population Genetics and the Future of Cancer Screening
Population genetics is changing how we think about cancer screening. This short report identifies ATM c.7374_7375insAlu as a founder pathogenic variant in French Canadians associated with increased risk of pancreatic and breast cancer. The broader point is clinical as much as genetic: populations with shared ancestry can carry recurrent disease-causing variants that may be overlooked […]
Molecular Sleuthing: Unmasking Hidden Lymphomas through Plasma DNA Sequencing (Contributed by Dr Sarah Huet)
Lymphomas are often difficult to diagnose when they present without clear tumors or detectable abnormalities on standard tests, leading to delays in treatment. This study highlights two patients in whom a blood test analyzing circulating tumor DNA (ctDNA) detected signs of an aggressive lymphoma months before conventional methods confirmed the diagnosis. By identifying ctDNA in […]
Long-read sequencing enables trio-assisted phasing of de novo variants in the imprinted gene MAGEL2 (Contributed by Dr Thomas Laver)
Schaaf-Yang syndrome is a rare genetic disorder affecting children that is caused by changes in the MAGEL2 gene but only if the change occurs in the version of the gene inherited from the father. Genetic diagnosis is often challenging because most MAGEL2 changes are new in the child (de novo), making it unclear which parental […]
Perspectives of adolescents and young adults with advanced cancer on complete genomic analysis in standard oncology care (Contributed by Lina Lankhorst)
This manuscript examines how AYAs with advanced cancer experience undergoing complete genomic analysis within standard oncology care. While this approach may refine diagnoses or point to personalised treatment options beyond routine pathways, its immediate clinical impact is often limited. Even so, AYAs value having the opportunity, as it reassures them that all possibilities have been […]
Comprehensive genotype-phenotype correlation analysis in 11 509 neonates carrying common deafness-associated pathogenic variants (Contributed by Jianjun Li)
Our study looked at more than 11,500 newborns who carry genetic variants associated with deafness. Although genetic testing identified hundreds of infants at high risk for hearing loss, standard newborn hearing screenings failed to detect most of these cases—either because the babies could hear normally at birth or because the hearing loss develops later in […]
CDK4 and CDK6 variants in patients with primary microcephaly lead to cell cycle defects and mitochondria-induced apoptosis (Contributed by Professor Mustafa Tekin)
This study explores why some children are born with very small head size (microcephaly) due to rare changes in the CDK4 or CDK6 genes. These genes normally help cells divide and grow. We found that when they do not work properly, cells struggle to multiply and instead become stressed. Rather than simply slowing down, the […]
Comprehensive evidence for the pathogenicity of the BRCA2 c.7847C>T (p.Ser2616Phe) variant specific to the Japanese population (Contributed by Dr. Kazuki Yamazawa)
Genetic testing for hereditary breast and ovarian cancer often finds DNA changes whose clinical meaning is unclear, leaving patients without clear guidance. In this study, we focused on a BRCA2 gene variant found mainly in Japanese people that has long been classified as a “variant of uncertain significance.” By combining nationwide family data with multiple […]
Colonoscopy Surveillance in Lynch Syndrome: What It Prevents and What It Doesn’t (Contributed by Dr. Richard S Houlston)
This paper re-evaluates how effectively regular colonoscopy protects people with Lynch syndrome, a common inherited cause of bowel cancer. While colonoscopy saves lives by detecting cancers at an early stage, large contemporary studies show it does not reliably prevent cancers from developing. This is because Lynch syndrome cancers can grow rapidly or arise without visible […]