Biomedical subjects

Brian J Shayota

Publications and source records attributed to Brian J Shayota.

2 recordsLinked to original sources

PubMed2026

Rapid genome sequencing identifies treatable conditions in non-intensive care unit hospitalized children.

PURPOSE: The utility of rapid genome sequencing (RGS) has been evaluated in pediatric intensive care unit (ICU) settings, but few studies have investigated its use in non-critically ill hospitalized children. Our study assesses the impact of RGS use in the non-ICU setting. METHODS: We analyzed RGS results obtained for hospitalized children from 2019 to 2023 and evaluated the impact on non-ICU patient care. Changes in management were determined via chart review of the first 30 days after testing. RESULTS: RGS was performed on 422 individuals: 339 ICU and 83 non-ICU. The diagnostic rate was 39% (32 of 83) in non-ICU and 35% (120 of 339) in ICU patients. Eighty-one percent of diagnostic RGS results in non-ICU patients had a management change within 30 days, and 56% (18 of 32) received a disease-targeted intervention, including medication or diet change, listing for transplant, or connection with a clinical trial. Of the children who received these intervention changes, the most common disease categories were metabolic (61%, 11 of 18) and epilepsy (22%, 4 of 18). CONCLUSION: RGS is effective at identifying treatable diagnoses in the non-ICU setting, with most patients experiencing a change in their care, and over half receiving disease-focused interventions. Our results support the utility of RGS in non-ICU hospitalized children and can impact providers' decision-making and payer coverage.

Genome sequencing↗

PubMed2026

Uncovering phenotypic expansion in AXIN2-related disorders through precision animal modeling.

PURPOSE: Heterozygous pathogenic variants in AXIN2 (HGNC: 904) cause oligodontia-colorectal cancer syndrome. We identified 5 individuals with de novo heterozygous variants [NM_004655.4:c.196G>A p.(Glu66Lys), c.197A>G p.(Glu66Gly), and c.199G>A p.(Gly67Arg)] in AXIN2. Common phenotypes among these individuals included ectodermal dysplasia, global developmental delay, microcephaly, and limb, ophthalmologic, and genitourinary abnormalities. METHODS: Structural modeling was performed to predict the impact of these variants on AXIN2. A prime editing N1 screen of mouse embryos was performed to test whether the p.Glu66Lys variant produces a phenotype. Drosophila models were used to test the effect of this variant on Wnt signaling. RESULTS: Structural modeling suggests that these variants disrupt AXIN2 binding to tankyrase, which regulates AXIN2 levels through poly-ADP-ribosylation. Heterozygous (p.Glu66Lys) mouse embryos were perinatally lethal with soft palate clefts and skeletal abnormalities. Modeling of the p.Glu66Lys variant in the Drosophila wing suggests gain-of-function or dominant-negative activity compared to reference AXIN2. CONCLUSION: Specific variants in the tankyrase-binding domain of AXIN2 are pathogenic, leading to phenotypic expansion with potential context-dependent effects on AXIN2 function and Wnt signaling. The N1 modeling strategy used to demonstrate variant pathogenicity may be beneficial for resolving other heterozygous variants associated with congenital anomalies.

AXIN2↗