Evidence map›Paper›PMID 38909119›Full record

ArticleJournal of neurology2024

De novo variants in immune regulatory genes in Down syndrome regression disorder.

Saba Jafarpour, Abhik K Banerjee, Mellad M Khoshnood, Benjamin N Vogel, Natalie K Boyd, Lina Nguyen, Rebecca Partridge, Stephanie L Santoro, Grace Y Gombolay, Kristen S Fisher and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Saba JafarpourDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Abhik K BanerjeeDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Mellad M KhoshnoodDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Benjamin N VogelDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Natalie K BoydDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Lina NguyenDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA.
Rebecca PartridgeVirginia Mason Health System, Issaquah, WA, USA.
Stephanie L SantoroDepartment of Genetics, Harvard Medical School, Boston, MA, USA.
Grace Y GombolayDivision of Neurology, Department of Pediatrics, Emory School of Medicine, and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Kristen S FisherDepartment of Neurology, Baylor College of Medicine, Houston, TX, USA.
Diego Real de AsuaAdult Down Syndrome Outpatient Clinic, Department of Internal Medicine, Fundación de Investigación Biomédica, Hospital Universitario de La Princesa, Madrid, Spain.
Maria Carmen Del OrtegaDepartment of Psychiatry, Clinica Universidad de Navarra, Madrid, Spain.
Cathy FranklinDepartment of Psychiatry, Mater Research Institute, University of Queensland, Brisbane, Australia.
Michael S RafiiDepartment of Neurology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA.
Jonathan D SantoroDivision of Neurology, Department of Pediatrics, Children's Hospital Los Angeles, 4650 Sunset Blvd, Mailstop 82, Los Angeles, CA, 90027, USA. santoroj@usc.edu.ORCID http://orcid.org/0000-0002-8350-8234

Funding

Mechanistic investigation of therapies for Down Syndrome Regression DisorderR61HD109748 · NICHD · UNIVERSITY OF COLORADO DENVER · PI ESPINOSA, JOAQUIN M., SANNAR, ELISE M · 2022 to 2023
$1.5M
Non-invasive biometric screening for cerebrovascular disorders in persons with Down syndrome.K23HL155898 · NHLBI · CHILDREN'S HOSPITAL OF LOS ANGELES · PI SANTORO, JONATHAN DOUGLAS · 2021 to 2025
$1.3M
National Institute of Child Health and Human Development R611HD109748NHLBI NIH HHS K23 HL155898NICHD NIH HHS R61 HD109748
6 · The paper itself

Abstract

backgroundDown Syndrome Regression Disorder (DSRD) is a rare and poorly understood disorder of the central nervous system, characterized by acute or subacute neuropsychiatric symptoms in previously healthy individuals with Down syndrome (DS). Many patients exhibit immunotherapy-responsiveness, indicative of immune dysregulation as a potential underlying etiology. While hypotheses are emerging regarding the role of interferon signaling in DSRD and other autoimmune conditions associated with DS, it is unclear why a small subset of individuals with DS develop DSRD. The aim of this study was to investigate genes of immune regulation in persons with DSRD.

methodsThis study included individuals with DSRD aged 10-30 years with trio exome sequencing performed during the diagnostic work up. Descriptive statistics and univariate analysis (Chi-square and Fisher's exact test) were used to describe and compare the characteristics of individuals with and without variants.

resultsForty-one individuals with DSRD had trio exome sequencing results. Eight (20%) had heterozygous de novo variants of immune regulatory genes, with four variants being pathogenic or likely pathogenic (UNC13D, XIAP, RNASEH2A, and DNASE1L3). All genes harboring pathogenic variants were associated with interferon type-1 inflammatory response. Individuals harboring variants were more likely to have a preceding trigger (p = 0.03, 95% CI 1.21-97.06), rapid clinical decline in less than 1 month (p = 0.01, 95% CI 1.67-52.06), and MRI abnormalities (p < 0.001, 95% CI 4.89-527.71). DISCUSSION: A distinct subset of individuals with DSRD exhibited pathogenic variants in immune regulation genes associated with interferon-mediated inflammatory response, coinciding with previously established links between these genes and interferonopathies such as Aicardi-Goutieres syndrome. Our observations suggest that these variants might potentially contribute to the development of DSRD in individuals with DS.

Indexed as

Down SyndromeAdolescentAdultChildExome SequencingFemaleHumansMaleYoung AdultDown syndromeGeneInterferonRegressionVariant

Identifiers

PMID38909119
PMCPMC11319504

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.