Variants in the WDR45 Gene Within the OPA-2 Locus Associate With Isolated X-Linked Optic Atrophy.

Purpose: To describe clinical and molecular findings of two families with X-linked optic atrophy and present two new pathogenic variants in the WDR45 gene. Methods: Case series and molecular analysis of two families of Jewish Ashkenazi descent with early onset bilateral optic atrophy. Whole-exome sequencing (WES) and bioinformatic analysis were performed, followed by Sanger sequencing and segregation analysis. Results: In both families, male siblings (three in family 1, two in family 2) had early-onset isolated bilateral optic atrophy. The sibling's healthy mother (and in the second family also one healthy sister) had a mild presentation, suggesting a carrier state and an X-linked inheritance pattern. All participants were otherwise healthy, apart from mild learning disabilities and autism spectrum disorder in two siblings of the second family. Variants in known optic atrophy genes were excluded. Analysis revealed a point variant in the WDR45 gene-a missense variant in the first family, NM_001029896.2:c.107C>A; NP_001025067.1:p.Pro36His (variant ID: 1704205), and a splice site variant in the second family, NM_001029896.2:c.236-1G>T; NP_009006.2:p.Val80Leu (variant ID: 1704204), located on Xp11.23 (OPA2 locus). Both variants are novel and predicted as pathogenic. In both families, the variant was seen with full segregation with the disease, occurring in all affected male participants and in one allele of the carrier females, as well as none of the healthy participants. Conclusions: Among two families with isolated X-linked optic atrophy, molecular analysis revealed novel variants in the WDR45 gene in full segregation with the disease. This gene resides within the OPA2 locus, previously described to associate with X-linked optic atrophy. Taken together, these findings suggest that certain pathogenic variants in the WDR45 gene are associated with isolated X-linked optic atrophy.

Exploring the characteristics of successful prehospital trauma care teams: Insights from military trauma care simulations.

BACKGROUND: Trauma care teams play a crucial role in determining the outcomes of trauma victims. The composition and training of these teams can vary. Our study seeks to examine the characteristics of successful military Advanced Life Support (ALS) teams and the factors that affect them. METHODS: A retrospective study was conducted at the Israel Defense Force (IDF) Military Medical Academy throughout 2021, where prehospital medical teams were observed in trauma care simulations. Teams were led by ALS providers (military physicians or paramedics) trained in IDF Military Trauma Life Support. Demographic and training data were collected. Teams were categorized into high or subpar performance groups based on simulation scores. Specific skills were assessed by trauma instructors using a points system. Scores were compared between the groups and analyzed for correlations with demographic and training data. RESULTS: Overall, 63 team simulations were analyzed, with teams led by a military paramedic in 78% of simulations. The mean overall simulation performance was 81% ±6.2, and there were no differences in scores of single or multicasualty simulations. A total 3% of the teams achieved successful results and were more likely to have a paramedic as the ALS provider ( p = 0.028). A sensitivity analysis excluding physicians was conducted and showed that high-performance teams had significantly higher skill assessments for primary survey ( p = 0.004), injury recognition ( p = 0.002), exposure ( p = 0.006), adherence to clinical practice guidelines ( p = 0.032), and medical device use ( p = 0.002). CONCLUSION: Our study found that ALS provider is associated with overall simulation performance in prehospital ALS teams, with military paramedics more likely to be successful. These findings have implications for the training and staffing of prehospital ALS teams, suggesting that teams should be composed accordingly and that training should focus on skills affected by the ALS provider type. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.