This November, as genomic medicine continues to evolve, EJHG brings together studies that reflect its expansion into healthcare systems, biobanking, collaborative platforms, and patient-centred perspectives.

Rare genetic conditions and genotype–phenotype associations are a strong focus in this issue. MYBPC3 is a leading genetic cause of hypertrophic cardiomyopathy. Fabiani et al. show age- and sex-dependent variable expressivity, with males having earlier onset and more severe phenotypes [1]. Scheidecker et al. broaden the MYH10-associated phenotype by identifying six individuals with eye malformations and craniofacial features without neurodevelopmental involvement, distinguishing it from Baraitser–Winter cerebrofrontofacial syndrome [2]. Leduc et al. analyse 49 new and 207 previously reported Townes-Brocks syndrome cases with SALL1 variants, highlighting variability in the classic triad [3]. They also report that the location of the mutation influences clinical features, with some regions being linked to deafness and limb anomalies and as well as a lower risk of kidney problems.

Expanding the focus on developmental and structural phenotypes, Houdayer et al. report 27 new cases of ARID2-related disorder, characterised by developmental delay, short stature, and dysmorphic features, and point towards a distinctive DNA methylation episignature [4]. In parallel, Smail et al. examine the phenotypic spectrum of conditions associated with variants in Polycomb (PcG) and Trithorax (TrxG) gene complexes, two key epigenetic regulators [5]. Analysing 462 patients, they highlight both convergence and heterogeneity in growth, limb, craniofacial, and behavioural features, underscoring pathway-level parallels alongside individual variability in these epigenetic developmental disorders.

The role of genomic testing in rare diseases is increasingly recognized, though its implementation varies. Mackley et al. provide a comprehensive review across specialties, discussing strategies for effective integration [6]. Building on this, recent studies highlight the clinical utility of genome sequencing in this issue. Kang et al. identify genetic etiologies in 65% of 768 Chinese patients with hearing loss using whole exome sequencing, expanding the spectrum with 40 novel variants with markedly higher yields in severe hearing loss [7]. Similarly, Lindelöf et al. demonstrate that genome sequencing, combined with detailed phenotyping, achieves a 72% diagnostic yield in affected fetuses, with four additional VUS suspected to be causative based on phenotype [8].

The growing role of biobanking in research and rare diseases is undeniable. Nurm et al. identify 17 individuals at high risk of Wilson disease through biobank analysis, most showing low ceruloplasmin and copper levels and early neurodegenerative signs [9]. Their findings highlight underdiagnosis, while illustrating the potential for early, personalised management. Beyond clinical applications, understanding the use of biological samples can further enhance this support. Tupasela et al. emphasise the need for standards, strategic development, and secure integration of tissue samples with health data [10]. Complementing this, Huremagic et al. introduce MINDDS-Connect, a federated platform linking biobanks across institutions, maintaining privacy and improving access to support large-scale, standardised mental health research in line with EU Open Science policies [11].

Genetic counselling remains essential for families navigating inherited conditions. Swinkels et al. indicate that CCGCTG-interrupted intermediate CTG repeats (37–43 units) in the DMPK gene neither segregate with disease nor expand intergenerationally, with important implications for myotonic dystrophy counselling [12]. Continuing with molecular mechanisms, Kandettu et al. report bi-allelic MRPS2 variants in two unrelated individuals with metabolic decompensation and hypoglycemia [13]. Functional zebrafish studies confirm the gene’s role in mitochondrial translation and OXPHOS, expanding its clinical spectrum.

Determining severity in genetic diseases can be challenging, and perceptions of severity may differ between healthcare professionals and patients. Sajko et al. propose a three-tier model based on patient-centred perspectives, revealing that parents consider shortened lifespan more severe than intellectual disability compared to healthcare professionals [14]. These perceptions of severity influence pregnancy termination decisions, underscoring the role of patient perspectives in decision-making. Of course, knowledge and understanding of genetic concepts are key determinants in decision-making about genetic conditions. Integrating genetics into school curricula is a crucial step toward fostering genetic literacy. However, this can be particularly challenging for specific groups, such as students with intellectual disabilities, where educators play a central role. Jackaman et al. highlight the need for tailored pedagogy, teacher training, and accessible resources to achieve this goal [15].

Systematic reviews remain a cornerstone of research synthesis, and critical appraisal is crucial for producing high-quality systematic reviews. Lindsay et al. examine 149 systematic reviews in genetics and reveal that while most mention appraisal tools, the transparency and practical use of these assessments are limited [16]. This analysis highlights the ongoing need to strengthen critical appraisal practices and reporting in genetic research.