Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders
by treatment before symptom onset. In many genetic diseases, however, outcomes remain …

The transition from analog to digital technologies in clinical laboratory genomics is ushering
in an era of “big data” in ways that will exceed human capacity to rapidly and reproducibly …

Purpose Variants of uncertain significance (VUS) are a common result of diagnostic genetic
testing and can be difficult to manage with potential misinterpretation and downstream costs …

Importance Newborn genome sequencing (NBSeq) can detect infants at risk for treatable
disorders currently undetected by conventional newborn screening. Despite broad …

DNA sequencing data continue to progress toward longer reads with increasingly lower
sequencing error rates. We focus on the critical problem of mapping, or aligning, low …

Importance Understanding the causes of infant mortality shapes public health, surveillance,
and research investments. However, the association of single-locus (mendelian) genetic …

Molecular diagnostics is a cornerstone of modern precision medicine, broadly understood
as tailoring an individual's treatment, follow‐up, and care based on molecular data. In rare …

Importance Genomic testing in infancy guides medical decisions and can improve health
outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene …

Rare genetic disorders affect as many as 3%–5% of all babies born. Approximately 10,000
such disorders have been identified or hypothesized to exist. Treatment is supportive except …

Results: In total, 260 indeterminate PALF patients from 19 countries were recruited between
2011 and 2022, of whom 59 had recurrent PALF. WES established a genetic diagnosis in …