Genomic sequencing in acutely ill infants: what will it take to demonstrate clinical value?
Genet Med. 2019 Feb;21(2):269-271. doi: 10.1038/s41436-018-0124-3. Epub 2018 Aug 13. NO ABSTRACT PMID:30100610 | PMC:PMC6691721 | DOI:10.1038/s41436-018-0124-3
Mutations in LNPK, Encoding the Endoplasmic Reticulum Junction Stabilizer Lunapark, Cause a Recessive Neurodevelopmental Syndrome
Am J Hum Genet. 2018 Aug 2;103(2):296-304. doi: 10.1016/j.ajhg.2018.06.011. Epub 2018 Jul 19. ABSTRACT The dynamic shape of the endoplasmic reticulum (ER) is a reflection of its wide variety of critical cell biological functions. Consequently, perturbation of ER-shaping proteins can cause a range of human phenotypes. Here, we describe three affected children (from two consanguineous […]
Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration
Nat Genet. 2018 Aug;50(8):1093-1101. doi: 10.1038/s41588-018-0166-0. Epub 2018 Jul 16. ABSTRACT Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Here, we identify biallelic truncating mutations in CTNNA2, encoding αN-catenin, in patients with a distinct recessive form of pachygyria. CTNNA2 was expressed in human cerebral cortex, and its loss […]
Meta-analysis of the diagnostic and clinical utility of genome and exome sequencing and chromosomal microarray in children with suspected genetic diseases
NPJ Genom Med. 2018 Jul 9;3:16. doi: 10.1038/s41525-018-0053-8. eCollection 2018. ABSTRACT Genetic diseases are leading causes of childhood mortality. Whole-genome sequencing (WGS) and whole-exome sequencing (WES) are relatively new methods for diagnosing genetic diseases, whereas chromosomal microarray (CMA) is well established. Here we compared the diagnostic utility (rate of causative, pathogenic, or likely pathogenic genotypes […]
Whole exome sequencing reveals HSPA1L as a genetic risk factor for spontaneous preterm birth
PLoS Genet. 2018 Jul 12;14(7):e1007394. doi: 10.1371/journal.pgen.1007394. eCollection 2018 Jul. ABSTRACT Preterm birth is a leading cause of morbidity and mortality in infants. Genetic and environmental factors play a role in the susceptibility to preterm birth, but despite many investigations, the genetic basis for preterm birth remain largely unknown. Our objective was to identify rare, […]
Implementation, adoption, and utility of family health history risk assessment in diverse care settings: evaluating implementation processes and impact with an implementation framework
Genet Med. 2019 Feb;21(2):331-338. doi: 10.1038/s41436-018-0049-x. Epub 2018 Jun 6. ABSTRACT PURPOSE: This paper describes the implementation outcomes associated with integrating a family health history-based risk assessment and clinical decision support platform within primary care clinics at four diverse healthcare systems. METHODS: A type III hybrid implementation-effectiveness trial. Uptake and implementation processes were evaluated using […]
Sdha+/- Rats Display Minimal Muscle Pathology Without Significant Behavioral or Biochemical Abnormalities
J Neuropathol Exp Neurol. 2018 Aug 1;77(8):665-672. doi: 10.1093/jnen/nly042. ABSTRACT Mitochondrial diseases (MDs) result from alteration of the mitochondrial respiratory chain (MRC) function. Despite the prevalence of MDs in the population, the paucity of animal models available limits the understanding of these disorders. Mutations in SDHA, a gene that codes for the alpha subunit of […]
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 […]