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, […]
Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation
Sci Transl Med. 2019 Apr 24;11(489):eaat6177. doi: 10.1126/scitranslmed.aat6177. ABSTRACT By informing timely targeted treatments, rapid whole-genome sequencing can improve the outcomes of seriously ill children with genetic diseases, particularly infants in neonatal and pediatric intensive care units (ICUs). The need for highly qualified professionals to decipher results, however, precludes widespread implementation. We describe a platform […]
Effect of Sociodemographic Factors on Uptake of a Patient-Facing Information Technology Family Health History Risk Assessment Platform
Appl Clin Inform. 2019 Mar;10(2):180-188. doi: 10.1055/s-0039-1679926. Epub 2019 Mar 13. ABSTRACT OBJECTIVE: Investigate sociodemographic differences in the use of a patient-facing family health history (FHH)-based risk assessment platform. METHODS: In this large multisite trial with a diverse patient population, we evaluated the relationship between sociodemographic factors and FHH health risk assessment uptake using an […]
Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy
Nat Commun. 2019 Feb 12;10(1):707. doi: 10.1038/s41467-018-07067-3. ABSTRACT Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report […]
Blacklisting variants common in private cohorts but not in public databases optimizes human exome analysis
Proc Natl Acad Sci U S A. 2019 Jan 15;116(3):950-959. doi: 10.1073/pnas.1808403116. Epub 2018 Dec 27. ABSTRACT Computational analyses of human patient exomes aim to filter out as many nonpathogenic genetic variants (NPVs) as possible, without removing the true disease-causing mutations. This involves comparing the patient’s exome with public databases to remove reported variants inconsistent […]
Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria
Genet Med. 2019 Aug;21(8):1851-1867. doi: 10.1038/s41436-018-0403-z. Epub 2018 Dec 14. ABSTRACT PURPOSE: Phenylketonuria (PKU) is a rare metabolic disorder that requires life-long management to reduce phenylalanine (Phe) concentrations within the recommended range. The availability of pegvaliase (PALYNZIQ™, an enzyme that can metabolize Phe) as a new therapy necessitates the provision of guidance for its use. […]
MAB21L1 loss of function causes a syndromic neurodevelopmental disorder with distinctive cerebellar, ocular, craniofacial and genital features (COFG syndrome)
J Med Genet. 2019 May;56(5):332-339. doi: 10.1136/jmedgenet-2018-105623. Epub 2018 Nov 28. ABSTRACT BACKGROUND: Putative nucleotidyltransferase MAB21L1 is a member of an evolutionarily well-conserved family of the male abnormal 21 (MAB21)-like proteins. Little is known about the biochemical function of the protein; however, prior studies have shown essential roles for several aspects of embryonic development including […]