De Novo ZMYND8 variants result in an autosomal dominant neurodevelopmental disorder with cardiac malformations
Genet Med. 2022 Aug 1:S1098-3600(22)00803-6. doi: 10.1016/j.gim.2022.06.001. Online ahead of print. ABSTRACT PURPOSE: ZMYND8 encodes a multidomain protein that serves as a central interactive hub for coordinating critical roles in transcription regulation, chromatin remodeling, regulation of super-enhancers, DNA damage response and tumor suppression. We delineate a novel neurocognitive disorder caused by variants in the ZMYND8 […]
Analysis of somatic mutations in 131 human brains reveals aging-associated hypermutability
Science. 2022 Jul 29;377(6605):511-517. doi: 10.1126/science.abm6222. Epub 2022 Jul 28. ABSTRACT We analyzed 131 human brains (44 neurotypical, 19 with Tourette syndrome, 9 with schizophrenia, and 59 with autism) for somatic mutations after whole genome sequencing to a depth of more than 200×. Typically, brains had 20 to 60 detectable single-nucleotide mutations, but ~6% of […]
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 […]
Ultra Rapid Whole Genome Sequencing: A Paradigm Shift in the Pre-Transplant Evaluation of Neonatal Acute Liver Failure
Liver Transpl. 2022 Jul 21. doi: 10.1002/lt.26547. Online ahead of print. NO ABSTRACT PMID:35861277 | DOI:10.1002/lt.26547
Combined MEK and JAK/STAT3 pathway inhibition effectively decreases SHH medulloblastoma tumor progression
Commun Biol. 2022 Jul 14;5(1):697. doi: 10.1038/s42003-022-03654-9. ABSTRACT Medulloblastoma (MB) is the most common primary malignant pediatric brain cancer. We recently identified novel roles for the MEK/MAPK pathway in regulating human Sonic Hedgehog (SHH) MB tumorigenesis. The MEK inhibitor, selumetinib, decreased SHH MB growth while extending survival in mouse models. However, the treated mice ultimately […]
Bi-allelic loss-of-function variants in PPFIBP1 cause a neurodevelopmental disorder with microcephaly, epilepsy, and periventricular calcifications
Am J Hum Genet. 2022 Jul 7:S0002-9297(22)00261-0. doi: 10.1016/j.ajhg.2022.06.008. Online ahead of print. ABSTRACT PPFIBP1 encodes for the liprin-β1 protein, which has been shown to play a role in neuronal outgrowth and synapse formation in Drosophila melanogaster. By exome and genome sequencing, we detected nine ultra-rare homozygous loss-of-function variants in 16 individuals from 12 unrelated […]
Neonatal familial hemophagocytic lymphohistiocytosis diagnosed with ultrarapid whole-genome sequencing
Pediatr Blood Cancer. 2022 Jul 7:e29871. doi: 10.1002/pbc.29871. Online ahead of print. NO ABSTRACT PMID:35796407 | DOI:10.1002/pbc.29871
Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission
Nature. 2022 Jul 7. doi: 10.1038/s41586-022-05049-6. Online ahead of print. ABSTRACT As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases1-3. SARS-CoV-2 RNA […]
Unbiased mosaic variant assessment in sperm: a cohort study to test predictability of transmission
Elife. 2022 Jul 5;11:e78459. doi: 10.7554/eLife.78459. ABSTRACT BACKGROUND: De novo mutations underlie individually rare but collectively common pediatric congenital disorders. Some of these mutations can also be detected in tissues and from cells in a parent, where their abundance and tissue distribution can be measured. We previously reported that a subset of these mutations is […]
Random Field Modeling of Multi-trait Multi-locus Association for Detecting Methylation Quantitative Trait Loci
Bioinformatics. 2022 Jul 4:btac443. doi: 10.1093/bioinformatics/btac443. Online ahead of print. ABSTRACT MOTIVATION: CpG sites within the same genomic region often share similar methylation patterns and tend to be co-regulated by multiple genetic variants that may interact with one another. RESULTS: We propose a multi-trait methylation random field (multi-MRF) method to evaluate the joint association between […]