Developmental and temporal characteristics of clonal sperm mosaicism

Cell. 2021 Aug 7:S0092-8674(21)00883-7. doi: 10.1016/j.cell.2021.07.024. Online ahead of print. ABSTRACT Throughout development and aging, human cells accumulate mutations resulting in genomic mosaicism and genetic diversity at the cellular level. Mosaic mutations present in the gonads can affect both the individual and the offspring and subsequent generations. Here, we explore patterns and temporal stability of […]

Postmortem whole-genome sequencing on a dried blood spot identifies a novel homozygous SUOX variant causing isolated sulfite oxidase deficiency

Cold Spring Harb Mol Case Stud. 2021 Jun 11;7(3):a006091. doi: 10.1101/mcs.a006091. Print 2021 Jun. ABSTRACT Rapid whole-genome sequencing (rWGS) has shown that genetic diseases are a common cause of infant mortality in neonatal intensive care units. Dried blood spots collected for newborn screening allow investigation of causes of infant mortality that were not diagnosed during […]

Measurement of genetic diseases as a cause of mortality in infants receiving whole genome sequencing

NPJ Genom Med. 2020 Nov 2;5:49. doi: 10.1038/s41525-020-00155-8. eCollection 2020. ABSTRACT Understanding causes of infant mortality shapes public health policy and prioritizes diseases for investments in surveillance, intervention and medical research. Rapid genomic sequencing has created a novel opportunity to decrease infant mortality associated with treatable genetic diseases. Herein, we sought to measure the contribution […]

Mortality in a neonate with molybdenum cofactor deficiency illustrates the need for a comprehensive rapid precision medicine system

Cold Spring Harb Mol Case Stud. 2020 Feb 3;6(1):a004705. doi: 10.1101/mcs.a004705. Print 2020 Feb. ABSTRACT Neonatal encephalopathy with seizures is a presentation in which rapid whole-genome sequencing (rWGS) has shown clinical utility and improved outcomes. We report a neonate who presented on the third day of life with seizures refractory to antiepileptic medications and neurologic […]

Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU

Pediatr Crit Care Med. 2019 Nov;20(11):1007-1020. doi: 10.1097/PCC.0000000000002056. ABSTRACT OBJECTIVES: Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU in the United States. Although individually rare, there are over 6,200 single-gene diseases, which may preclude a genetic diagnosis prior to ICU admission. Rapid whole genome sequencing is an emerging method […]

Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation

Sci Transl Med. 2019 Apr 24;11(489):eaat6177. doi: 10.1126/scitranslmed.aat6177. ABSTRACT By informing timely targeted treatments, rapid whole-genome sequencing can improve the outcomes of seriously ill children with genetic diseases, particularly infants in neonatal and pediatric intensive care units (ICUs). The need for highly qualified professionals to decipher results, however, precludes widespread implementation. We describe a platform […]

Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth

PLoS Genet. 2018 Jul 12;14(7):e1007394. doi: 10.1371/journal.pgen.1007394. eCollection 2018 Jul. ABSTRACT Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, […]

Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization

NPJ Genom Med. 2018 Apr 4;3:10. doi: 10.1038/s41525-018-0049-4. eCollection 2018. ABSTRACT Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. We report a retrospective cohort study […]

The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants

NPJ Genom Med. 2018 Feb 9;3:6. doi: 10.1038/s41525-018-0045-8. eCollection 2018. ABSTRACT Genetic disorders are a leading cause of morbidity and mortality in infants in neonatal and pediatric intensive care units (NICU/PICU). While genomic sequencing is useful for genetic disease diagnosis, results are usually reported too late to guide inpatient management. We performed an investigator-initiated, partially […]