Ayat Kadhi

Introduction: Brugada syndrome (BrS) is an inherited arrhythmia associated with an increased risk of sudden cardiac death. Although traditionally regarded as a primary cardiac channelopathy, pathogenic variants in SCN5A account for only 20%–30% of clinically diagnosed cases, leaving most patients genetically unresolved. Emerging evidence suggests that structural cardiac genes may also contribute to BrS susceptibility. We investigated the genetic basis of BrS in a consanguineous Lebanese family with three affected brothers. Methods and Results: Whole‐exome sequencing was performed in all affected individuals, followed by variant calling, annotation, and phenotype‐driven prioritization using Franklin (Genoox). Candidate variants were evaluated according to allele frequency, inheritance model, segregation, and ACMG/AMP classification. Evolutionary conservation, AlphaMissense prediction, protein domain annotation, and structural modeling were performed to assess the potential functional impact of the prioritized variant. Whole‐exome sequencing identified a rare homozygous CSRP3 missense variant (NM_003476.5:c.56 A > G; p.His19Arg) shared by all three affected siblings. Following exome‐wide filtering under a recessive inheritance model, CSRP3 represented the only rare homozygous coding variant, while no pathogenic or likely pathogenic variants were identified in established Brugada syndrome‐associated genes. The variant was absent from public population databases and an internal cohort of Lebanese exomes. His19 was highly conserved across vertebrate species, AlphaMissense classified the variant as likely pathogenic (score = 0.942), and structural modeling predicted alterations within the N‐terminal LIM domain that may affect protein stability and local residue interactions. Conclusions: Our findings nominate CSRP3 as a candidate susceptibility gene for Brugada syndrome and support the emerging role of structural cardiac genes in inherited arrhythmia syndromes. Although functional validation is required to establish causality, this study highlights the value of whole‐exome sequencing in consanguineous and underrepresented populations for identifying rare candidate variants contributing to BrS susceptibility.

Introduction: Recent advancements in genomic technologies have significantly improved the resolution of genetic variants driving rare genodermatoses, a heterogeneous group of inherited skin disorders caused by pathogenic variants affecting skin structure and function. However, many genodermatoses remain molecularly uncharacterized, particularly in Middle Eastern populations. Objectives: This study aimed to evaluate the diagnostic accuracy and inherent challenges of utilizing (WES) for genodermatoses within a Middle Eastern context. Methods: We performed WES on three unrelated Middle Eastern pediatric patients presenting with genodermatoses. Genetic variants were prioritized and adjudicated according to ClinVar and the American College of Medical Genetics and Genomics (ACMG) guidelines. Results: WES identified pathogenic variants in three pediatric cases presenting with genodermatoses. Findings included a GJB2 missense variant (c.148G>T; p.Asp50Asn) associated with keratitis–ichthyosis–deafness (KID) syndrome. This represents one of the first documented cases in a Middle Eastern population. Two additional patients presenting with epidermolysis bullosa harbored truncating variants in COL7A1 (c.497dup; p.Val168Glyfs12) and EXPH5 (c.5786del; p.Pro1929Leufs8), respectively; the latter also carried a KRT5 missense variant (c.1607G>A; p.Ser536Asn). Conclusions: WES is a robust diagnostic adjunct for resolving ambiguity in rare genodermatoses, though its efficacy remains contingent on the availability of regional genomic references. Within pediatric dermatology, systematic exome sequencing serves as a powerful facilitator for transitioning from clinical suspicion to definitive molecular characterization. Collectively, these findings highlight the essential role of regionally representative genomic datasets in the accurate interpretation of novel variants and the advancement of precision dermatology.

This chapter explores the critical intersection of climate change and the well-being of allied health professionals. With rising global temperatures and increasing frequency of extreme weather events, the healthcare sector faces significant challenges. These conditions exacerbate health risks for allied health professionals, who are already prone to occupational stressors such as shift work and burnout. The chapter highlights how climate change amplifies cardiovascular and metabolic disorders among healthcare workers, stressing the need for comprehensive workplace interventions. It further examines adaptive strategies for promoting sustainability, emphasising behavioural, technological, and policy-driven approaches. The role of allied health professionals in reducing healthcare’s environmental footprint is explored, as they lead efforts in energy-efficient practices, telehealth, and waste reduction. By fostering resilience and advocating for climate-conscious healthcare policies, allied health professionals are positioned to lead both environmental and health-related reforms. This may ensure long-term sustainability and improved health outcomes for their communities in alignment with the United Nations’ Sustainable Development Goals 3, 11, and 13.