Evidence map›Paper›PMID 35119225›Full record

ArticleMolecular genetics & genomic medicine2022

Comprehensive variant calling from whole-genome sequencing identifies a complex inversion that disrupts ZFPM2 in familial congenital diaphragmatic hernia.

Thomas J Nicholas, Najla Al-Sweel, Andrew Farrell, Rong Mao, Pinar Bayrak-Toydemir, Christine E Miller, Dawn Bentley, Rachel Palmquist, Barry Moore, Edgar J Hernandez and 17 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular genetics & genomic medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 30% of its field
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

7 citing papers in PubMed, 8 citations in OpenAlex.

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  5. Genome sequencing ofGenome research · 2023
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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

27 authors at 3 institutions in 1 country.

Thomas J NicholasDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.ORCID 0000-0002-4198-6414
Najla Al-SweelARUP Laboratories, Salt Lake City, USA.
Andrew FarrellDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Rong MaoARUP Laboratories, Salt Lake City, USA.
Pinar Bayrak-ToydemirARUP Laboratories, Salt Lake City, USA.
Christine E MillerARUP Laboratories, Salt Lake City, USA.
Dawn BentleyDivision of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.
Rachel PalmquistDivision of Pediatric Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.
Barry MooreDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Edgar J HernandezDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Michael J CormierDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Eric FredricksonARUP Laboratories, Salt Lake City, USA.
Katherine NobleARUP Laboratories, Salt Lake City, USA.
Shawn RynearsonDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Carson HoltDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Mary Anne KarrenDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Joshua L BonkowskyDivision of Pediatric Neurology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.ORCID 0000-0001-8775-147X
Martin Tristani-FirouziDivision of Pediatric Cardiology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.
Mark YandellDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Gabor MarthDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Aaron R QuinlanDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Luca BrunelliDivision of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.
Reha M ToydemirARUP Laboratories, Salt Lake City, USA.ORCID 0000-0002-0797-1999
Brian J ShayotaDivision of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.
John C CareyDivision of Medical Genetics, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.ORCID 0000-0002-6007-8518
Steven E BoydenDepartment of Human Genetics, Utah Center for Genetic Discovery, University of Utah, Salt Lake City, USA.
Sabrina Malone JenkinsDivision of Neonatology, Department of Pediatrics, University of Utah School of Medicine, Salt Lake City, USA.ORCID 0000-0001-8810-7619
University of Utah · USARUP Laboratories (United States) · USPrimary Children's Hospital · US

Funding

Utah Center for Clinical and Translational ScienceUL1TR002538 · NCATS · UNIVERSITY OF UTAH · PI HESS, RACHEL, MAJERSIK, JENNIFER JUHL · 2018 to 2022
$26.0M
From genomics to natural language processing: A protected environment for research computing in the health scienceS10OD021644 · OD · UNIVERSITY OF UTAH · PI CHEATHAM, THOMAS E. · 2017 to 2017
$494k
NCATS NIH HHS UL1 TR002538NIH HHS S10 OD021644
6 · The paper itself

Abstract

backgroundGenetic disorders contribute to significant morbidity and mortality in critically ill newborns. Despite advances in genome sequencing technologies, a majority of neonatal cases remain unsolved. Complex structural variants (SVs) often elude conventional genome sequencing variant calling pipelines and will explain a portion of these unsolved cases.

methodsAs part of the Utah NeoSeq project, we used a research-based, rapid whole-genome sequencing (WGS) protocol to investigate the genomic etiology for a newborn with a left-sided congenital diaphragmatic hernia (CDH) and cardiac malformations, whose mother also had a history of CDH and atrial septal defect.

resultsUsing both a novel, alignment-free and traditional alignment-based variant callers, we identified a maternally inherited complex SV on chromosome 8, consisting of an inversion flanked by deletions. This complex inversion, further confirmed using orthogonal molecular techniques, disrupts the ZFPM2 gene, which is associated with both CDH and various congenital heart defects.

conclusionsOur results demonstrate that complex structural events, which often are unidentifiable or not reported by clinically validated testing procedures, can be discovered and accurately characterized with conventional, short-read sequencing and underscore the utility of WGS as a first-line diagnostic tool.

Indexed as

Hernias, Diaphragmatic, CongenitalDNA-Binding ProteinsGenomicsHumansInfant, NewbornTranscription FactorsWhole Genome SequencingDNA-Binding ProteinsTranscription FactorsZFPM2 protein, human

Identifiers

PMID35119225
PMCPMC9000945
OpenAlexW4210243964

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.