Pathogenic variants in PIDD1 lead to an autosomal recessive neurodevelopmental disorder with pachygyria and psychiatric features
Eur J Hum Genet. 2021 Jun 24. doi: 10.1038/s41431-021-00910-0. Online ahead of print. ABSTRACT The PIDDosome is a multiprotein complex, composed by the p53-induced death domain protein 1 (PIDD1), the bipartite linker protein CRADD (also known as RAIDD) and the proform of caspase-2 that induces apoptosis in response to DNA damage. In the recent years, […]
Sperm mosaicism: implications for genomic diversity and disease
Trends Genet. 2021 Jun 19:S0168-9525(21)00139-6. doi: 10.1016/j.tig.2021.05.007. Online ahead of print. ABSTRACT While sperm mosaicism has few consequences for men, the offspring and future generations are unwitting recipients of gonadal cell mutations, often yielding severe disease. Recent studies, fueled by emergent technologies, show that sperm mosaicism is a common source of de novo mutations (DNMs) […]
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 […]
Mapping methylation quantitative trait loci in cardiac tissues nominates risk loci and biological pathways in congenital heart disease
BMC Genom Data. 2021 Jun 10;22(1):20. doi: 10.1186/s12863-021-00975-2. ABSTRACT BACKGROUND: Most congenital heart defects (CHDs) result from complex interactions among genetic susceptibilities, epigenetic modifications, and maternal environmental exposures. Characterizing the complex relationship between genetic, epigenetic, and transcriptomic variation will enhance our understanding of pathogenesis in this important type of congenital disorder. We investigated cis-acting effects […]
Project Baby Bear: Rapid precision care incorporating rWGS in 5 California children’s hospitals demonstrates improved clinical outcomes and reduced costs of care
Am J Hum Genet. 2021 May 29:S0002-9297(21)00192-0. doi: 10.1016/j.ajhg.2021.05.008. Online ahead of print. ABSTRACT Genetic disorders are a leading contributor to mortality in neonatal and pediatric intensive care units (ICUs). Rapid whole-genome sequencing (rWGS)-based rapid precision medicine (RPM) is an intervention that has demonstrated improved clinical outcomes and reduced costs of care. However, the feasibility […]
Rapid Sequencing-Based Diagnosis of Thiamine Metabolism Dysfunction Syndrome
N Engl J Med. 2021 Jun 3;384(22):2159-2161. doi: 10.1056/NEJMc2100365. NO ABSTRACT PMID:34077649 | DOI:10.1056/NEJMc2100365
Ending a diagnostic odyssey: Moving from exome to genome to identify cockayne syndrome
Mol Genet Genomic Med. 2021 Jun 2:e1623. doi: 10.1002/mgg3.1623. Online ahead of print. ABSTRACT BACKGROUND: Cockayne syndrome (CS) is a rare autosomal recessive disorder characterized by growth failure and multisystemic degeneration. Excision repair cross-complementation group 6 (ERCC6 OMIM: *609413) is the gene most frequently mutated in CS. METHODS: A child with pre and postnatal growth […]
Quantitative analysis of the natural history of prolidase deficiency: description of 17 families and systematic review of published cases
Genet Med. 2021 May 26. doi: 10.1038/s41436-021-01200-2. Online ahead of print. ABSTRACT PURPOSE: Prolidase deficiency is a rare inborn error of metabolism causing ulcers and other skin disorders, splenomegaly, developmental delay, and recurrent infections. Most of the literature is constituted of isolated case reports. We aim to provide a quantitative description of the natural history […]
Loss of C2orf69 defines a fatal autoinflammatory syndrome in humans and zebrafish that evokes a glycogen storage-associated mitochondriopathy
Am J Hum Genet. 2021 May 21:S0002-9297(21)00187-7. doi: 10.1016/j.ajhg.2021.05.003. Online ahead of print. ABSTRACT Human C2orf69 is an evolutionarily conserved gene whose function is unknown. Here, we report eight unrelated families from which 20 children presented with a fatal syndrome consisting of severe autoinflammation and progredient leukoencephalopathy with recurrent seizures; 12 of these subjects, whose […]
Implementing Rapid Whole Genome Sequencing in Critical Care: A Qualitative Study of Facilitators and Barriers to New Technology Adoption
J Pediatr. 2021 May 20:S0022-3476(21)00496-0. doi: 10.1016/j.jpeds.2021.05.045. Online ahead of print. ABSTRACT OBJECTIVE: To characterize the views of members of the multi-disciplinary team regarding the implementation of Rapid Whole Genome Sequencing (rWGS) as a first-tier test for critically ill children in diverse children’s hospital settings. STUDY DESIGN: Qualitative interviews informed by implementation science theory were […]