An online compendium of treatable genetic disorders
Am J Med Genet C Semin Med Genet. 2021 Mar;187(1):48-54. doi: 10.1002/ajmg.c.31874. Epub 2020 Dec 22. ABSTRACT More than 4,000 genes have been associated with recognizable Mendelian/monogenic diseases. When faced with a new diagnosis of a rare genetic disorder, health care providers increasingly turn to internet resources for information to understand the disease and direct […]
UBR7 functions with UBR5 in the Notch signaling pathway and is involved in a neurodevelopmental syndrome with epilepsy, ptosis, and hypothyroidism
Am J Hum Genet. 2021 Jan 7;108(1):134-147. doi: 10.1016/j.ajhg.2020.11.018. Epub 2020 Dec 18. ABSTRACT The ubiquitin-proteasome system facilitates the degradation of unstable or damaged proteins. UBR1-7, which are members of hundreds of E3 ubiquitin ligases, recognize and regulate the half-life of specific proteins on the basis of their N-terminal sequences (“N-end rule”). In seven individuals […]
De novo variants in SNAP25 cause an early-onset developmental and epileptic encephalopathy
Genet Med. 2020 Dec 10. doi: 10.1038/s41436-020-01020-w. Online ahead of print. ABSTRACT PURPOSE: This study aims to provide a comprehensive description of the phenotypic and genotypic spectrum of SNAP25 developmental and epileptic encephalopathy (SNAP25-DEE) by reviewing newly identified and previously reported individuals. METHODS: Individuals harboring heterozygous missense or loss-of-function variants in SNAP25 were assembled through […]
Metagenomic sequencing and evaluation of the host response in the pediatric aerodigestive population
Pediatr Pulmonol. 2021 Feb;56(2):516-524. doi: 10.1002/ppul.25198. Epub 2020 Dec 14. ABSTRACT OBJECTIVES: To assess the diagnostic utility of metagenomic sequencing in pediatric aerodigestive clinic patients being evaluated for chronic aspiration. We hypothesize that using a metagenomics platform will aid in the identification of microbes not found on standard culture. STUDY DESIGN AND METHODS: Twenty-four children […]
MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia
Nat Commun. 2020 Nov 30;11(1):6087. doi: 10.1038/s41467-020-19919-y. ABSTRACT Inositol polyphosphates are vital metabolic and secondary messengers, involved in diverse cellular functions. Therefore, tight regulation of inositol polyphosphate metabolism is essential for proper cell physiology. Here, we describe an early-onset neurodegenerative syndrome caused by loss-of-function mutations in the multiple inositol-polyphosphate phosphatase 1 gene (MINPP1). Patients are […]
Mutations in Spliceosomal Genes PPIL1 and PRP17 Cause Neurodegenerative Pontocerebellar Hypoplasia with Microcephaly
Neuron. 2021 Jan 20;109(2):241-256.e9. doi: 10.1016/j.neuron.2020.10.035. Epub 2020 Nov 20. ABSTRACT Autosomal-recessive cerebellar hypoplasia and ataxia constitute a group of heterogeneous brain disorders caused by disruption of several fundamental cellular processes. Here, we identified 10 families showing a neurodegenerative condition involving pontocerebellar hypoplasia with microcephaly (PCHM). Patients harbored biallelic mutations in genes encoding the spliceosome […]
Biallelic variants in HPDL, encoding 4-hydroxyphenylpyruvate dioxygenase-like protein, lead to an infantile neurodegenerative condition
Genet Med. 2021 Mar;23(3):524-533. doi: 10.1038/s41436-020-01010-y. Epub 2020 Nov 14. ABSTRACT PURPOSE: Dioxygenases are oxidoreductase enzymes with roles in metabolic pathways necessary for aerobic life. 4-hydroxyphenylpyruvate dioxygenase-like protein (HPDL), encoded by HPDL, is an orphan paralogue of 4-hydroxyphenylpyruvate dioxygenase (HPD), an iron-dependent dioxygenase involved in tyrosine catabolism. The function and association of HPDL with human […]
Editorial overview: Neurodevelopment Diseases and Neurogenetics pivot towards mechanisms and therapies
Curr Opin Genet Dev. 2020 Dec;65:iii-vii. doi: 10.1016/j.gde.2020.09.001. Epub 2020 Nov 8. NO ABSTRACT PMID:33176916 | DOI:10.1016/j.gde.2020.09.001
At the intersection of precision medicine and population health: an implementation-effectiveness study of family health history based systematic risk assessment in primary care
BMC Health Serv Res. 2020 Nov 7;20(1):1015. doi: 10.1186/s12913-020-05868-1. ABSTRACT BACKGROUND: Risk assessment is a precision medicine technique that can be used to enhance population health when applied to prevention. Several barriers limit the uptake of risk assessment in health care systems; and little is known about the potential impact that adoption of systematic risk […]
A Prospective Study of Parental Perceptions of Rapid Whole-Genome and -Exome Sequencing among Seriously Ill Infants
Am J Hum Genet. 2020 Nov 5;107(5):953-962. doi: 10.1016/j.ajhg.2020.10.004. ABSTRACT Rapid diagnostic genomic sequencing recently became feasible for infants in intensive care units (ICUs). However, research regarding parents’ perceived utility, adequacy of consent, and potential harms and benefits is lacking. Herein we report results of parental surveys of these domains from the second Newborn Sequencing […]