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 […]
One in seven pathogenic variants can be challenging to detect by NGS: an analysis of 450,000 patients with implications for clinical sensitivity and genetic test implementation
Genet Med. 2021 May 18. doi: 10.1038/s41436-021-01187-w. Online ahead of print. ABSTRACT PURPOSE: To evaluate the impact of technically challenging variants on the implementation, validation, and diagnostic yield of commonly used clinical genetic tests. Such variants include large indels, small copy-number variants (CNVs), complex alterations, and variants in low-complexity or segmentally duplicated regions. METHODS: An […]
Missense and truncating variants in CHD5 in a dominant neurodevelopmental disorder with intellectual disability, behavioral disturbances, and epilepsy
Hum Genet. 2021 May 4. doi: 10.1007/s00439-021-02283-2. Online ahead of print. ABSTRACT Located in the critical 1p36 microdeletion region, the chromodomain helicase DNA-binding protein 5 (CHD5) gene encodes a subunit of the nucleosome remodeling and deacetylation (NuRD) complex required for neuronal development. Pathogenic variants in six of nine chromodomain (CHD) genes cause autosomal dominant neurodevelopmental […]
Loss of function mutations in GEMIN5 cause a neurodevelopmental disorder
Nat Commun. 2021 May 7;12(1):2558. doi: 10.1038/s41467-021-22627-w. ABSTRACT GEMIN5, an RNA-binding protein is essential for assembly of the survival motor neuron (SMN) protein complex and facilitates the formation of small nuclear ribonucleoproteins (snRNPs), the building blocks of spliceosomes. Here, we have identified 30 affected individuals from 22 unrelated families presenting with developmental delay, hypotonia, and […]
Discriminating Bacterial and Viral Infection Using a Rapid Host Gene Expression Test
Crit Care Med. 2021 Apr 28. doi: 10.1097/CCM.0000000000005085. Online ahead of print. ABSTRACT OBJECTIVES: Host gene expression signatures discriminate bacterial and viral infection but have not been translated to a clinical test platform. This study enrolled an independent cohort of patients to describe and validate a first-in-class host response bacterial/viral test. DESIGN: Subjects were recruited […]
Expanding the genotypic spectrum of ACTG2-related visceral myopathy
Cold Spring Harb Mol Case Stud. 2021 Apr 21:mcs.a006085. doi: 10.1101/mcs.a006085. Online ahead of print. ABSTRACT Visceral myopathies (VMs) encompass a spectrum of disorders characterized by chronic disruption of gastrointestinal function, with or without urinary system involvement. Pathogenic missense variation in smooth muscle gamma-actin gene (ACTG2) is associated with autosomal dominant VM. Whole genome sequencing […]
Rapid whole genome sequencing impacts care and resource utilization in infants with congenital heart disease
NPJ Genom Med. 2021 Apr 22;6(1):29. doi: 10.1038/s41525-021-00192-x. ABSTRACT Congenital heart disease (CHD) is the most common congenital anomaly and a major cause of infant morbidity and mortality. While morbidity and mortality are highest in infants with underlying genetic conditions, molecular diagnoses are ascertained in only ~20% of cases using widely adopted genetic tests. Furthermore, […]
Rare deleterious mutations of HNRNP genes result in shared neurodevelopmental disorders
Madelyn A Gillentine Genome Med. 2021 Apr 19;13(1):63. doi: 10.1186/s13073-021-00870-6. ABSTRACT BACKGROUND: With the increasing number of genomic sequencing studies, hundreds of genes have been implicated in neurodevelopmental disorders (NDDs). The rate of gene discovery far outpaces our understanding of genotype-phenotype correlations, with clinical characterization remaining a bottleneck for understanding NDDs. Most disease-associated Mendelian genes […]