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 […]
Primary Cilia and Brain Wiring, Connecting the Dots
Dev Cell. 2019 Dec 16;51(6):661-663. doi: 10.1016/j.devcel.2019.11.017. ABSTRACT Primary cilia function as cellular signaling hubs, integrating multiple signaling pathways. Patients with the ciliopathy Joubert syndrome have been suggested to have axonal tract defects. In this issue of Developmental Cell, Guo et al. (2019) demonstrate a ciliary signaling requirement for axonal tract development and connectivity through […]
Combination of whole exome sequencing and animal modeling identifies TMPRSS9 as a candidate gene for autism spectrum disorder
Hum Mol Genet. 2020 Feb 1;29(3):459-470. doi: 10.1093/hmg/ddz305. ABSTRACT Autism spectrum disorders are associated with some degree of developmental regression in up to 30% of all cases. Rarely, however, is the regression so extreme that a developmentally advanced young child would lose almost all ability to communicate and interact with her surroundings. We applied trio […]
Mutations in PDLIM5 are rare in dilated cardiomyopathy but are emerging as potential disease modifiers
Mol Genet Genomic Med. 2020 Feb;8(2):e1049. doi: 10.1002/mgg3.1049. Epub 2019 Dec 27. ABSTRACT BACKGROUND: A causal genetic mutation is found in 40% of families with dilated cardiomyopathy (DCM), leaving a large percentage of families genetically unsolved. This prevents adequate counseling and clear recommendations in these families. We aim to identify novel genes or modifiers associated […]
Autism risk in offspring can be assessed through quantification of male sperm mosaicism
Nat Med. 2020 Jan;26(1):143-150. doi: 10.1038/s41591-019-0711-0. Epub 2019 Dec 23. ABSTRACT De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the […]
Correction: DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract
Genet Med. 2020 Apr;22(4):821. doi: 10.1038/s41436-019-0732-6. ABSTRACT An amendment to this paper has been published and can be accessed via a link at the top of the paper. PMID:31857706 | DOI:10.1038/s41436-019-0732-6
Gene-by-gene interactions associated with the risk of conotruncal heart defects
Mol Genet Genomic Med. 2020 Jan;8(1):e1010. doi: 10.1002/mgg3.1010. Epub 2019 Dec 18. ABSTRACT BACKGROUND: The development of conotruncal heart defects (CTDs) involves a complex relationship among genetic variants and maternal lifestyle factors. In this article, we focused on the interactions between 13 candidate genes within folate, homocysteine, and transsulfuration pathways for potential association with CTD […]
Diagnosis and treatment of a boy with IPEX syndrome presenting with diabetes in early infancy
Clin Case Rep. 2019 Sep 27;7(11):2123-2127. doi: 10.1002/ccr3.2438. eCollection 2019 Nov. ABSTRACT IPEX syndrome (Immune dysregulation, Polyendocrinopathy, X-linked) should be tested for in males under 6 months old presenting with diabetes, even without other IPEX features. Early diagnosis and bone marrow transplantation can improve outcomes. PMID:31788263 | PMC:PMC6878034 | DOI:10.1002/ccr3.2438
De novo and inherited variants in ZNF292 underlie a neurodevelopmental disorder with features of autism spectrum disorder
Genet Med. 2020 Mar;22(3):538-546. doi: 10.1038/s41436-019-0693-9. Epub 2019 Nov 14. ABSTRACT PURPOSE: Intellectual disability (ID) and autism spectrum disorder (ASD) are genetically heterogeneous neurodevelopmental disorders. We sought to delineate the clinical, molecular, and neuroimaging spectrum of a novel neurodevelopmental disorder caused by variants in the zinc finger protein 292 gene (ZNF292). METHODS: We ascertained a […]
Validation of a host response test to distinguish bacterial and viral respiratory infection
EBioMedicine. 2019 Oct;48:453-461. doi: 10.1016/j.ebiom.2019.09.040. Epub 2019 Oct 17. ABSTRACT BACKGROUND: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative […]