Comprehensive Profiling of DNA Repair Defects in Breast Cancer Identifies a Novel Class of Endocrine Therapy Resistance Drivers
Clin Cancer Res. 2018 Oct 1;24(19):4887-4899. doi: 10.1158/1078-0432.CCR-17-3702. Epub 2018 May 23. ABSTRACT Purpose: This study was undertaken to conduct a comprehensive investigation of the role of DNA damage repair (DDR) defects in poor outcome ER+ disease. Experimental Design: Expression and mutational status of DDR genes in ER+ breast tumors were correlated with proliferative response […]
Syndromic congenital myelofibrosis associated with a loss-of-function variant in RBSN
Blood. 2018 Aug 9;132(6):658-662. doi: 10.1182/blood-2017-12-824433. Epub 2018 May 21. ABSTRACT Publisher’s Note: There is a Blood Commentary on this article in this issue. PMID:29784638 | PMC:PMC6085991 | DOI:10.1182/blood-2017-12-824433
Paternally inherited cis-regulatory structural variants are associated with autism
Science. 2018 Apr 20;360(6386):327-331. doi: 10.1126/science.aan2261. ABSTRACT The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural […]
Pegvaliase for the treatment of phenylketonuria: Results of a long-term phase 3 clinical trial program (PRISM)
Mol Genet Metab. 2018 May;124(1):27-38. doi: 10.1016/j.ymgme.2018.03.006. Epub 2018 Mar 31. ABSTRACT BACKGROUND: Phenylketonuria (PKU) is caused by phenylalanine hydroxylase (PAH) deficiency that results in phenylalanine (Phe) accumulation. Pegvaliase, PEGylated recombinant Anabaena variabilis phenylalanine ammonia lyase (PAL), converts Phe to trans-cinnamic acid and ammonia, and is a potential enzyme substitution therapy to lower blood Phe […]
Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization
NPJ Genom Med. 2018 Apr 4;3:10. doi: 10.1038/s41525-018-0049-4. eCollection 2018. ABSTRACT Genetic disorders are a leading cause of morbidity and mortality in infants. Rapid whole-genome sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants. We report a retrospective cohort study […]
Early life experience shapes neural genome
Science. 2018 Mar 23;359(6382):1330-1331. doi: 10.1126/science.aat3977. NO ABSTRACT PMID:29567692 | DOI:10.1126/science.aat3977
The case for early use of rapid whole-genome sequencing in management of critically ill infants: late diagnosis of Coffin-Siris syndrome in an infant with left congenital diaphragmatic hernia, congenital heart disease, and recurrent infections
Cold Spring Harb Mol Case Stud. 2018 Jun 1;4(3):a002469. doi: 10.1101/mcs.a002469. Print 2018 Jun. ABSTRACT Congenital diaphragmatic hernia (CDH) results from incomplete formation of the diaphragm leading to herniation of abdominal organs into the thoracic cavity. CDH is associated with pulmonary hypoplasia, congenital heart disease, and pulmonary hypertension. Genetically, it is associated with aneuploidies, chromosomal […]
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 […]