HOX genes, a family of conserved transcription factors, are critical for reproductive tract development and endometrial functionality. This review highlights the molecular underpinnings of HOXA10/HOXA11 in reproductive health and their dysregulation in benign pathologies associated with infertility, such as endometriosis, adenomyosis, and endometrial polyps. These genes are dynamically regulated by estrogen and progesterone, with peak expression during the secretory phase of the menstrual cycle when implantation takes place. The molecular mechanisms underlying their action include the modulation of extracellular matrix (ECM) remodeling via metalloproteinases, cytokines like leukemia inhibitory factor, and cell adhesion molecules such as β3-integrin, all of which are essential for the differentiation of epithelial and stromal cells, as well as for trophoblast invasion. Aberrant HOX gene expression, driven by DNA hypermethylation or altered histone acetylation, compromises endometrial receptivity and implantation. For instance, reduced HOXA10 expression in endometriosis stems from hypermethylation and chronic inflammation, disrupting immune modulation and cytokine signaling. Similarly, adenomyosis alters HOXA11-regulated ECM remodeling and β3-integrin expression, impairing embryo attachment. Furthermore, regulatory pathways involving vitamin D and retinoic acid offer promising therapeutic avenues pathways, as they enhance HOXA10/HOXA11 expression and endometrial receptivity. This review underscores the critical molecular roles of HOXA10/HOXA11 genes as biomarkers and therapeutic targets to optimize fertility outcomes and address reproductive pathologies.

PTEN Hamartoma Tumour Syndrome (PHTS) encompasses diverse clinical phenotypes, including Cowden syndrome (CS), Bannayan–Riley–Ruvalcaba syndrome (BRRS), Proteus syndrome (PS), and Proteus-like syndrome. This autosomal dominant genetic predisposition with high penetrance arises from heterozygous germline variants in the PTEN tumour suppressor gene, leading to dysregulation of the PI3K/AKT/mTOR signalling pathway, which promotes the overgrowth of multiple and heterogenous tissue types. Clinical presentations of CS range from benign and malignant disorders, affecting nearly every system within the human body. CS is the most diagnosed syndrome among the PHTS group, notwithstanding its weak incidence (1:200,000), for which it is considered rare, and its precise incidence remains unknown among other important factors. The literature is notably inconsistent in reporting the frequencies and occurrences of these disorders, adding an element of bias and uncertainty when looking back at the available research. In this review, we aimed to highlight the significant disparities found in various studies concerning CS and to review the clinical manifestations encountered in CS patients. Furthermore, we intended to emphasize the great significance of early diagnosis as patients will benefit from a longer lifespan while being unceasingly advised and supported by a multidisciplinary team.

Background/Objectives: Radiotherapy is a cornerstone in the treatment of breast cancer, yet its use is frequently accompanied by skin toxicities that vary in severity and timing among patients. The objective of this meta-analysis is to systematically evaluate the pooled impact of genetic variations on the risk and severity of acute and late skin side effects from radiotherapy in breast cancer patients. Materials and Methods: A systematic literature search was conducted across PubMed, Embase, and Scopus to identify studies published between 2014 and 2024 that examined associations between genetic polymorphisms and radiotherapy-induced skin toxicity. Studies were selected based on predefined inclusion and exclusion criteria, and data were synthesized using a random-effects meta-analysis model. The risk of bias was evaluated using the ROBINS-I tool, and publication bias was assessed through funnel plots and Egger’s test. Results: A total of 11 studies involving breast cancer patients were included, identifying associations between various gene polymorphisms and skin toxicity. The pooled analysis revealed that patients with specific genetic variants had a 53% increased risk of acute skin side effects and a 44% increased risk of late effects. Notable implicated genes included XRCC2, IFNG, ATM, TGFB1, and PER3. Significant heterogeneity and publication bias were noted across studies, warranting cautious interpretation. Conclusions: This meta-analysis highlights the role of genetic variation in predicting radiotherapy-induced skin toxicity in breast cancer patients. These findings support the future development of predictive biomarkers and personalized radiotherapy strategies to minimize treatment-related toxicity.

Primary ciliary dyskinesia (PCD), a rare disorder, is genetically varied. Mutations in proteins involved in the structure, function, or assembly of cilia are known to determine situs inversus, male infertility, and chronic destructive airway disease. PCD is inherited by an autosomal recessive pattern of inheritance in most cases. Nonetheless, patterns of autosomal dominant and X-linked inheritance have been mentioned. A history of recurrent upper and lower respiratory tract infections raised clinical suspicion of primary ciliary dyskinesia in a 10-year-old patient. Genetic tests were performed using next-generation sequencing technology (Illumina NextGen) with the multiplex ligation-dependent probe amplification technique for primary ciliopathies and syndromes subject to differential diagnosis. Genetic testing identified two pathogenic variants, not previously associated with a case report in the literature, c.7727A>G (p.Asp2576Gly) and c.8578G>A (p.Gly2860Ser), within the DNAH11 gene, which is associated with autosomal recessive PCD. The result also reported mutations in other genes involved in autosomal recessive PCD (DNAH8, DNAH9 and ZMYND10), which were classified as variants with uncertain clinical significance. Transmission electron microscopy of respiratory cilia and nasal nitric oxide measurement cannot be used to diagnose PCD in patients with DNAH11 mutations because the structure of cilia is normal, and the levels of NO are not constantly low. High-speed video microscopy analysis can be helpful because DNAH11 mutations cause a distinct phenotype of PCD. Nevertheless, the mutation analysis of various PCD-causing genes remains the easiest to conduct and with good results. Genetic research on PCD has identified a number of significant ciliary genes in recent years, offering fresh perspectives on the molecular processes underlying cilia assembly and function. This facilitates the development of new methods for the diagnosis, prevention, and treatment of PCD. However, because it is a highly complex and heterogeneous disease, the field of gene diagnosis and therapy in PCD is still in its infancy.

Human ageing and longevity are increasingly understood as biologically integrated and heterogeneous processes shaped by interactions among genetic susceptibility, epigenetic remodelling, and environmental modulation. This narrative review examines these interconnections within a nutrigenomic framework, with particular emphasis on how inherited variation and epigenetic plasticity may influence responses to ageing-related interventions. A structured literature search was conducted in PubMed, Scopus, Web of Science, and Embase, focusing on English-language studies published during the last 10 years. The review was organized into three major domains: (i) genetic determinants of longevity, (ii) epigenetic mechanisms of ageing, and (iii) intervention-responsive pathways relevant to precision geroscience. Current evidence supports a polygenic model of longevity in which loci such as FOXO3 and APOE show the most consistent human associations, while telomere maintenance, insulin/IGF-1 and mTOR signalling, sirtuins, Klotho, inflammatory mediators, and DNA repair remain biologically important but variably supported at the variant level. Epigenetic mechanisms, including DNA methylation drift, epigenetic clocks, histone modifications, chromatin remodelling, heterochromatin loss, and non-coding RNA regulation, provide an environmentally responsive interface linking genetic background to ageing phenotypes. Nutritional, pharmacological, behavioural, and circadian interventions converge on overlapping molecular pathways involving AMPK, mTOR, FOXO, sirtuins, autophagy, mitochondrial maintenance, and inflammatory signalling, although human evidence remains heterogeneous and biomarker modulation should not be equated with clinically meaningful slowing of organismal ageing. Overall, this review highlights the value of integrating genetics, epigenetics, and intervention biology to support a more cautious and translationally relevant model of healthy ageing. It also underscores the need for precision nutrigeroscience approaches that account for tissue context, baseline physiology, and inter-individual molecular variability.

Background. Breast cancer remains a leading cause of cancer-related death among women, with genetic mutations playing a key role. While high-penetrance mutations are well-studied, moderate-to-low-penetrance mutations, which present challenges in clinical decision-making and patient outcomes, are less understood. This study explores the quality of life of breast cancer patients with moderate-penetrance mutations, focusing on the psychosocial and physical consequences of mastectomy and reconstruction to improve patient-centered care. Materials and Methods. A cohort of 620 breast cancer patients treated at Regina Maria Private Health Network, Bucharest, between January 2022 and July 2024 was identified. From this group, 61 patients were selected based on the following criteria: (1) meeting NCCN genetic testing guidelines, (2) carrying moderate-to-low-penetrance mutations, (3) undergoing bilateral mastectomy with double reconstruction, and (4) agreeing to complete a modified version of the BREAST-Q questionnaire. Genetic testing was performed using a 125-gene next-generation sequencing panel. Statistical analyses included non-parametric tests to examine group differences and correlations. Results. Significant correlations were found between several factors. Emotional distress was positively correlated with concerns for family, while couple relationships and financial burden showed a strong positive association. Negative correlations were found between couple relationships and self-concept. Distress levels varied, with “Interference with personal relationships” causing more distress than “Impact on employment”, and financial burden causing more distressing than impact on sexuality. Conclusions. Prophylactic mastectomy significantly reduces cancer risk for women with moderate-penetrance mutations. This study highlights the relationship between surgical choices and quality-of-life factors, advancing personalized prevention strategies and emphasizing patient-centered care.