A Randomized, Controlled Trial of the Analytic and Diagnostic Performance of Singleton and Trio, Rapid Genome and Exome Sequencing in Ill Infants
Am J Hum Genet. 2019 Oct 3;105(4):719-733. doi: 10.1016/j.ajhg.2019.08.009. Epub 2019 Sep 26. ABSTRACT The second Newborn Sequencing in Genomic Medicine and Public Health study was a randomized, controlled trial of the effectiveness of rapid whole-genome or -exome sequencing (rWGS or rWES, respectively) in seriously ill infants with diseases of unknown etiology. Here we report […]
The mitochondrial carrier Citrin plays a role in regulating cellular energy during carcinogenesis
Oncogene. 2020 Jan;39(1):164-175. doi: 10.1038/s41388-019-0976-2. Epub 2019 Aug 28. ABSTRACT Citrin, encoded by SLC25A13 gene, is an inner mitochondrial transporter that is part of the malate-aspartate shuttle, which regulates the NAD+/NADH ratio between the cytosol and mitochondria. Citrullinemia type II (CTLN-II) is an inherited disorder caused by germline mutations in SLC25A13, manifesting clinically in growth […]
Bi-allelic GOT2 Mutations Cause a Treatable Malate-Aspartate Shuttle-Related Encephalopathy
Am J Hum Genet. 2019 Sep 5;105(3):534-548. doi: 10.1016/j.ajhg.2019.07.015. Epub 2019 Aug 15. ABSTRACT Early-infantile encephalopathies with epilepsy are devastating conditions mandating an accurate diagnosis to guide proper management. Whole-exome sequencing was used to investigate the disease etiology in four children from independent families with intellectual disability and epilepsy, revealing bi-allelic GOT2 mutations. In-depth metabolic […]
Agenesis of the putamen and globus pallidus caused by recessive mutations in the homeobox gene GSX2
Brain. 2019 Oct 1;142(10):2965-2978. doi: 10.1093/brain/awz247. ABSTRACT Basal ganglia are subcortical grey nuclei that play essential roles in controlling voluntary movements, cognition and emotion. While basal ganglia dysfunction is observed in many neurodegenerative or metabolic disorders, congenital malformations are rare. In particular, dysplastic basal ganglia are part of the malformative spectrum of tubulinopathies and X-linked […]
Hypospadias Prevalence and Trends in International Birth Defect Surveillance Systems, 1980-2010
Eur Urol. 2019 Oct;76(4):482-490. doi: 10.1016/j.eururo.2019.06.027. Epub 2019 Jul 9. ABSTRACT BACKGROUND: Hypospadias is a common male birth defect that has shown widespread variation in reported prevalence estimates. Many countries have reported increasing trends over recent decades. OBJECTIVE: To analyze the prevalence and trends of hypospadias for 27 international programs over a 31-yr period. DESIGN, […]
NSUN2 introduces 5-methylcytosines in mammalian mitochondrial tRNAs
Nucleic Acids Res. 2019 Sep 19;47(16):8720-8733. doi: 10.1093/nar/gkz559. ABSTRACT Expression of human mitochondrial DNA is indispensable for proper function of the oxidative phosphorylation machinery. The mitochondrial genome encodes 22 tRNAs, 2 rRNAs and 11 mRNAs and their post-transcriptional modification constitutes one of the key regulatory steps during mitochondrial gene expression. Cytosine-5 methylation (m5C) has been […]
DYRK1A-related intellectual disability: a syndrome associated with congenital anomalies of the kidney and urinary tract
Genet Med. 2019 Dec;21(12):2755-2764. doi: 10.1038/s41436-019-0576-0. Epub 2019 Jul 2. ABSTRACT PURPOSE: Haploinsufficiency of DYRK1A causes a recognizable clinical syndrome. The goal of this paper is to investigate congenital anomalies of the kidney and urinary tract (CAKUT) and genital defects (GD) in patients with DYRK1A variants. METHODS: A large database of clinical exome sequencing (ES) […]
Rapid Whole Genome Sequencing Has Clinical Utility in Children in the PICU
Pediatr Crit Care Med. 2019 Nov;20(11):1007-1020. doi: 10.1097/PCC.0000000000002056. ABSTRACT OBJECTIVES: Genetic disorders are a leading contributor to mortality in the neonatal ICU and PICU in the United States. Although individually rare, there are over 6,200 single-gene diseases, which may preclude a genetic diagnosis prior to ICU admission. Rapid whole genome sequencing is an emerging method […]
Neonatal diabetes mellitus due to a novel variant in the INS gene
Cold Spring Harb Mol Case Stud. 2019 Aug 1;5(4):a004085. doi: 10.1101/mcs.a004085. Print 2019 Aug. ABSTRACT Neonatal diabetes mellitus (NDM) is a rare condition that presents with diabetes in the first few months of life. The treatment of NDM may differ depending on the genetic etiology, with numerous studies showing the benefit of sulfonylurea therapy in […]
Further phenotypic characterization of Kaufman oculocerebrofacial syndrome: report of five new cases and literature review
Clin Dysmorphol. 2019 Oct;28(4):175-183. doi: 10.1097/MCD.0000000000000282. ABSTRACT Kaufman oculocerebrofacial syndrome is a rare autosomal recessive disorder caused by biallelic variants in UBE3B. Kaufman oculocerebrofacial syndrome is characterized by a recognizable pattern of malformations including moderate to severe intellectual disability, growth deficiency, microcephaly and a distinctive facial gestalt. Common craniofacial features include short upslanting palpebral fissures, […]