Clinical RNA sequencing clarifies variants of uncertain significance identified by prior testing.

Purpose: Sequencing-based genetic testing often identifies variants of uncertain significance (VUS) or fails to detect pathogenic variants altogether. We evaluated the utility of RNA sequencing (RNA-seq) to clarify VUS or identify missing variants in a clinical setting.

Methods: Over a 2-year period, genetics providers at a single institution referred 26 cases for clinical RNA-seq.

3-hour genome sequencing and targeted analysis to rapidly assess genetic risk.

Purpose: Rapid genetic testing in the critical care setting may guide diagnostic evaluation, direct therapies, and help families and care providers make informed decisions about goals of care. We tested whether a simplified DNA extraction and library preparation process would enable us to perform ultra-rapid assessment of genetic risk for a Mendelian condition, based on information from an affected sibling, using long-read genome sequencing and targeted analysis.

Methods: Following extraction of DNA from cord blood and rapid library preparation, genome sequencing was performed on an Oxford Nanopore PromethION.

Procedural volume is linearly associated with mortality, major complications, and readmissions in patients undergoing malignant brain tumor resection.

Purpose: Improved outcomes have been noted in patients undergoing malignant brain tumor resection at high-volume centers. Studies have arbitrarily chosen high-volume dichotomous cutoffs and have not evaluated volume-outcome associations at specific institutional procedural volumes. We sought to establish the continuous association of volume with patient outcomes and identify cutoffs significantly associated with mortality, major complications, and readmissions.

Novel insights into the phenotypic spectrum and pathogenesis of Hardikar syndrome.

Purpose: Hardikar syndrome (HS, MIM #301068) is a female-specific multiple congenital anomaly syndrome characterized by retinopathy, orofacial clefting, aortic coarctation, biliary dysgenesis, genitourinary malformations, and intestinal malrotation. We previously showed that heterozygous nonsense and frameshift variants in MED12 cause HS. The phenotypic spectrum of disease and the mechanism by which MED12 variants cause disease is unknown.