Publications by authors named "M L Freckmann"
Purpose: To characterize the diagnostic and clinical outcomes of a cohort of critically ill infants and children with suspected mitochondrial disorders (MD) undergoing ultrarapid genomic testing as part of a national program.
Methods: Ultrarapid genomic sequencing was performed in 454 families (genome sequencing: n = 290, exome sequencing +/- mitochondrial DNA sequencing: n = 164). In 91 individuals, MD was considered, prompting analysis using an MD virtual gene panel.
Article Synopsis
- - The Acute Care Genomics program in Australia offered whole-genome sequencing to 290 families of critically ill children over 2 years, achieving an average result time of 2.9 days and a diagnostic yield of 47%.
- - Further analysis and advanced sequencing methods led to 19 additional diagnoses, increasing the overall diagnostic yield to 54%, with various genetic issues identified.
- - Among the diagnosed patients, 77% experienced changes in critical care management, significantly influencing treatment options, surgeries, and palliative care in 60% of cases, highlighting the effectiveness of integrating advanced genomic approaches into regular diagnostic practices.
Article Synopsis
- Whole genome sequencing (WGS) shows better diagnostic results for Mendelian disorders than whole exome sequencing (WES), with a diagnostic yield of 34% in previously WES-negative families compared to 18% for reanalyzed WES.
- The cost-effectiveness analysis revealed that using WGS alone has a higher incremental cost per additional diagnosis (AU$41,916) compared to WES followed by WGS (AU$36,710) and WGS as a first-line test (AU$29,708).
- Despite WGS's superior diagnostic ability, the choice between WES and WGS ultimately hinges on specific clinical needs, local resources, and testing availability, as WES with reanalysis offers lower
Article Synopsis
- * Mice with the mutation show severe developmental issues, including early embryonic death and disrupted heartbeat, while patient-derived heart cells demonstrate normal function with minor defects, indicating that the disease's severity can be reduced.
- * Another variant in a different actin-binding protein appears to mitigate the lethal effects of the original mutation, suggesting that genetic factors can provide resilience against harmful mutations that may otherwise lead to serious health issues.
Purpose: Genetic variants causing aberrant premessenger RNA splicing are increasingly being recognized as causal variants in genetic disorders. In this study, we devise standardized practices for polymerase chain reaction (PCR)-based RNA diagnostics using clinically accessible specimens (blood, fibroblasts, urothelia, biopsy).
Methods: A total of 74 families with diverse monogenic conditions (31% prenatal-congenital onset, 47% early childhood, and 22% teenage-adult onset) were triaged into PCR-based RNA testing, with comparative RNA sequencing for 19 cases.