Reclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing
JAMA Netw Open. 2023 Feb 1;6(2):e2254069. doi: 10.1001/jamanetworkopen.2022.54069. ABSTRACT IMPORTANCE: Understanding the causes of infant mortality shapes public health, surveillance, and research investments. However, the association of single-locus (mendelian) genetic diseases with infant mortality is poorly understood. OBJECTIVE: To determine the association of genetic diseases with infant mortality. DESIGN, SETTING, AND PARTICIPANTS: This cohort study […]
25: A Multicenter Cohort Analysis of Rapid Genome Sequencing in the PICU
Critical Care Medicine 51(1):p 13, January 2023. Genetic disorders contribute significantly to morbidity and mortality in pediatric critical care. Diagnostic rapid whole genome sequencing (rWGS) has dramatically impacted care in neonatal intensive care units (ICU). There remains a population of undiagnosed patients with rare genetic diseases who present critically ill to the pediatric ICU (PICU) […]
Further delineation of the CWC27-associated spliceosomeopathy: Case report and review of the literature
Am J Med Genet A. 2023 Jan 31. doi: 10.1002/ajmg.a.63134. Online ahead of print. ABSTRACT Pre-mRNA splicing factors are crucial in regulating transcript diversity, by removing introns from eukaryotic transcripts, an essential step in gene expression. Splicing of pre-mRNA is catalyzed by spliceosomes. CWC27 is a cyclophilin associated with spliceosome, in which genetic defects of […]
The Genomic landscape of short tandem repeats across multiple ancestries
PLoS One. 2023 Jan 26;18(1):e0279430. doi: 10.1371/journal.pone.0279430. eCollection 2023. ABSTRACT Short Tandem Repeats (STRs) have been found to play a role in a myriad of complex traits and genetic diseases. We examined the variability in the lengths of over 850,000 STR loci in 996 children with suspected genetic disorders and 1,178 parents across six separate […]
Are we prepared to deliver gene-targeted therapies for rare diseases?
Am J Med Genet C Semin Med Genet. 2023 Jan 24. doi: 10.1002/ajmg.c.32029. Online ahead of print. ABSTRACT The cost and time needed to conduct whole-genome sequencing (WGS) have decreased significantly in the last 20 years. At the same time, the number of conditions with a known molecular basis has steadily increased, as has the […]
TMEM161B modulates radial glial scaffolding in neocortical development
Proc Natl Acad Sci U S A. 2023 Jan 24;120(4):e2209983120. doi: 10.1073/pnas.2209983120. Epub 2023 Jan 20. ABSTRACT TMEM161B encodes an evolutionarily conserved widely expressed novel 8-pass transmembrane protein of unknown function in human. Here we identify TMEM161B homozygous hypomorphic missense variants in our recessive polymicrogyria (PMG) cohort. Patients carrying TMEM161B mutations exhibit striking neocortical PMG […]
Stem Cell-Based Organoid Models of Neurodevelopmental Disorders
Biol Psychiatry. 2023 Jan 24:S0006-3223(23)00039-2. doi: 10.1016/j.biopsych.2023.01.012. Online ahead of print. ABSTRACT The past decade has seen an explosion in the identification of genetic causes of neurodevelopmental disorders, including Mendelian, de novo, and somatic factors. These discoveries provide opportunities to understand cellular and molecular mechanisms as well as potential gene-gene and gene-environment interactions to support […]
Insights into the perinatal phenotype of Kabuki syndrome in infants identified by genome-wide sequencing
Am J Med Genet A. 2023 Jan 18. doi: 10.1002/ajmg.a.63097. Online ahead of print. ABSTRACT Increasing use of unbiased genomic sequencing in critically ill infants can expand understanding of rare diseases such as Kabuki syndrome (KS). Infants diagnosed with KS through genome-wide sequencing performed during the initial hospitalization underwent retrospective review of medical records. Human […]
Reversibility and developmental neuropathology of linear nevus sebaceous syndrome caused by dysregulation of the RAS pathway
Cell Rep. 2023 Jan 14;42(1):112003. doi: 10.1016/j.celrep.2023.112003. Online ahead of print. ABSTRACT Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous disorder caused by somatic gain-of-function mutations in KRAS or HRAS. LNSS brains have neurodevelopmental defects, including cerebral defects and epilepsy; however, its pathological mechanism and potentials for treatment are largely unclear. We show that introduction […]
Novel Approach to Improve the Identification of the Bleeding Phenotype in Noonan Syndrome and Related RASopathies
J Pediatr. 2023 Jan 13:S0022-3476(23)00019-7. doi: 10.1016/j.jpeds.2022.12.036. Online ahead of print. ABSTRACT OBJECTIVES: To characterize bleeding phenotype in Noonan Syndrome, to test the utility of following national guidelines in detecting this phenotype, to evaluate thromboelastography (TEG) as a diagnostic tool and to evaluate the cohort for genotype-phenotype correlations. STUDY DESIGN: Participants with a clinical diagnosis […]