Unsupervised Analysis of Transcriptomics in Bacterial Sepsis Across Multiple Datasets Reveals Three Robust Clusters
Crit Care Med. 2018 Jun;46(6):915-925. doi: 10.1097/CCM.0000000000003084. ABSTRACT OBJECTIVES: To find and validate generalizable sepsis subtypes using data-driven clustering. DESIGN: We used advanced informatics techniques to pool data from 14 bacterial sepsis transcriptomic datasets from eight different countries (n = 700). SETTING: Retrospective analysis. SUBJECTS: Persons admitted to the hospital with bacterial sepsis. INTERVENTIONS: None. […]
Acute liver failure in neonates with undiagnosed hereditary fructose intolerance due to exposure from widely available infant formulas
Mol Genet Metab. 2018 Apr;123(4):428-432. doi: 10.1016/j.ymgme.2018.02.016. Epub 2018 Feb 27. ABSTRACT Hereditary fructose intolerance (HFI) is an autosomal recessive disorder caused by aldolase B (ALDOB) deficiency resulting in an inability to metabolize fructose. The toxic accumulation of intermediate fructose-1-phosphate causes multiple metabolic disturbances, including postprandial hypoglycemia, lactic acidosis, electrolyte disturbance, and liver/kidney dysfunction. The […]
A community approach to mortality prediction in sepsis via gene expression analysis
Nat Commun. 2018 Feb 15;9(1):694. doi: 10.1038/s41467-018-03078-2. ABSTRACT Improved risk stratification and prognosis prediction in sepsis is a critical unmet need. Clinical severity scores and available assays such as blood lactate reflect global illness severity with suboptimal performance, and do not specifically reveal the underlying dysregulation of sepsis. Here, we present prognostic models for 30-day […]
The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants
NPJ Genom Med. 2018 Feb 9;3:6. doi: 10.1038/s41525-018-0045-8. eCollection 2018. ABSTRACT Genetic disorders are a leading cause of morbidity and mortality in infants in neonatal and pediatric intensive care units (NICU/PICU). While genomic sequencing is useful for genetic disease diagnosis, results are usually reported too late to guide inpatient management. We performed an investigator-initiated, partially […]
Defining the phenotypic spectrum of SLC6A1 mutations
Epilepsia. 2018 Feb;59(2):389-402. doi: 10.1111/epi.13986. Epub 2018 Jan 8. ABSTRACT OBJECTIVE: Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients. METHODS: We collected 24 SLC6A1 probands and 6 affected family members. Four […]
Response to Metcalfe et al
Genet Med. 2018 Sep;20(9):1093. doi: 10.1038/gim.2017.208. NO ABSTRACT PMID:29240079 | DOI:10.1038/gim.2017.208
Response to Newman et al
Genet Med. 2017 Dec;19(12):10.1038/gim.2017.164. doi: 10.1038/gim.2017.164. Epub 2017 Oct 26. NO ABSTRACT PMID:29215644 | PMC:PMC7787267 | DOI:10.1038/gim.2017.164
The humanistic burden of Pompe disease: are there still unmet needs? A systematic review
BMC Neurol. 2017 Nov 22;17(1):202. doi: 10.1186/s12883-017-0983-2. ABSTRACT BACKGROUND: Humanistic burden considers the impact of an illness on a patient’s health-related quality of life (HRQoL), activities of daily living (ADL), caregiver health, and caregiver QoL. Humanistic burden also considers treatment satisfaction and adherence to treatment regimens. Pompe disease is an autosomal recessive, progressive, multisystemic neuromuscular […]
Mutations in GPAA1, Encoding a GPI Transamidase Complex Protein, Cause Developmental Delay, Epilepsy, Cerebellar Atrophy, and Osteopenia
Am J Hum Genet. 2017 Nov 2;101(5):856-865. doi: 10.1016/j.ajhg.2017.09.020. ABSTRACT Approximately one in every 200 mammalian proteins is anchored to the cell membrane through a glycosylphosphatidylinositol (GPI) anchor. These proteins play important roles notably in neurological development and function. To date, more than 20 genes have been implicated in the biogenesis of GPI-anchored proteins. GPAA1 […]
Pyruvate dehydrogenase complex-E2 deficiency causes paroxysmal exercise-induced dyskinesia
Neurology. 2017 Nov 28;89(22):2297-2298. doi: 10.1212/WNL.0000000000004689. Epub 2017 Nov 1. NO ABSTRACT PMID:29093066 | PMC:PMC5705245 | DOI:10.1212/WNL.0000000000004689