Phenotypic screening models for rapid diagnosis of genetic variants and discovery of personalized therapeutics

Mol Aspects Med. 2022 Nov 18:101153. doi: 10.1016/j.mam.2022.101153. Online ahead of print. ABSTRACT Precision medicine strives for highly individualized treatments for disease under the notion that each individual’s unique genetic makeup and environmental exposures imprints upon them not only a disposition to illness, but also an optimal therapeutic approach. In the realm of rare disorders, […]

Rapid Whole Genome Sequencing in Critically Ill Neonates Enables Precision Medicine Pipeline

J Pers Med. 2022 Nov 18;12(11):1924. doi: 10.3390/jpm12111924. ABSTRACT Rapid genome sequencing in critically ill infants is increasingly identified as a crucial test for providing targeted and informed patient care. We report the outcomes of a pilot study wherein eight critically ill neonates received rapid whole genome sequencing with parental samples in an effort to […]

Autosomal recessive LRP1-related syndrome featuring cardiopulmonary dysfunction, bone dysmorphology, and corneal clouding

Cold Spring Harb Mol Case Stud. 2022 Oct 28;8(6):a006169. doi: 10.1101/mcs.a006169. Print 2022 Oct. ABSTRACT We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including […]

Approaches to long-read sequencing in a clinical setting to improve diagnostic rate

Sci Rep. 2022 Oct 9;12(1):16945. doi: 10.1038/s41598-022-20113-x. ABSTRACT Over the past decade, advances in genetic testing, particularly the advent of next-generation sequencing, have led to a paradigm shift in the diagnosis of molecular diseases and disorders. Despite our present collective ability to interrogate more than 90% of the human genome, portions of the genome have […]

A genome sequencing system for universal newborn screening, diagnosis, and precision medicine for severe genetic diseases

Am J Hum Genet. 2022 Aug 18:S0002-9297(22)00355-X. doi: 10.1016/j.ajhg.2022.08.003. Online ahead of print. ABSTRACT Newborn screening (NBS) dramatically improves outcomes in severe childhood disorders by treatment before symptom onset. In many genetic diseases, however, outcomes remain poor because NBS has lagged behind drug development. Rapid whole-genome sequencing (rWGS) is attractive for comprehensive NBS because it […]

An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases

Nat Commun. 2022 Jul 26;13(1):4057. doi: 10.1038/s41467-022-31446-6. While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for […]

Better and Faster is Cheaper

Hum Mutat. 2022 Jun 20. doi: 10.1002/humu.24422. Online ahead of print. ABSTRACT The rapid pace of advancement in genomic sequencing technology has recently reached a new milestone, with a record-setting time to molecular diagnosis of a mere eight hours. The catalyst behind this achievement is the accumulation of evidence indicating that quicker results more often […]

The Role of Genome Sequencing in Neonatal Intensive Care Units

Annu Rev Genomics Hum Genet. 2022 Jun 8. doi: 10.1146/annurev-genom-120921-103442. Online ahead of print. ABSTRACT Genetic diseases disrupt the functionality of an infant’s genome during fetal-neonatal adaptation and represent a leading cause of neonatal and infant mortality in the United States. Due to disease acuity, gene locus and allelic heterogeneity, and overlapping and diverse clinical […]