Evidence map›Paper›PMID 26025024›Full record

ArticleCirculation. Cardiovascular genetics2015

Loss of Function Mutations in NNT Are Associated With Left Ventricular Noncompaction.

Matthew N Bainbridge, Erica E Davis, Wen-Yee Choi, Amy Dickson, Hugo R Martinez, Min Wang, Huyen Dinh, Donna M Muzny, Ricardo Pignatelli, Nicholas Katsanis and 3 more

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

Article in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.

  1. Pooled it
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  14. Loss ofInternational journal of molecular sciences · 2021
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  16. Zebrafish Heart Failure Models.Frontiers in cell and developmental biology · 2021
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  19. Life science alliance · 2020
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

Matthew N BainbridgeFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Erica E DavisFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Wen-Yee ChoiFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Amy DicksonFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Hugo R MartinezFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Min WangFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Huyen DinhFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Donna M MuznyFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Ricardo PignatelliFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Nicholas KatsanisFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Eric BoerwinkleFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.).
Richard A GibbsFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.). agibbs@bcm.edu john.jefferies@cchmc.org.
John L JefferiesFrom the Human Genome Sequencing Center (M.N.B., M.W., H.D., D.M., E.B., R.G.), Department Pediatrics-Cardiology, Baylor College of Medicine, Houston, TX (H.R.M., R.P., J.L.J.); Codified Genomics, LLC, Houston, TX (M.N.B.); Center for Human Disease Modeling, Duke University Medical Center, Durham, NC (E.E.D., N.K.); and Department of Cell Biology, Duke University, Durham, NC (W.-Y.C., A.D.). agibbs@bcm.edu john.jefferies@cchmc.org.
Duke Medical Center · USDuke University Hospital · USID Genomics (United States) · US

Funding

The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
NHGRI NIH HHS 5 U54 HG003273NHGRI NIH HHS U54 HG003273
6 · The paper itself

Abstract

backgroundLeft ventricular noncompaction (LVNC) is an autosomal-dominant, genetically heterogeneous cardiomyopathy with variable severity, which may co-occur with cardiac hypertrophy. METHODS AND

resultsHere, we generated whole exome sequence data from multiple members from 5 families with LVNC. In 4 of 5 families, the candidate causative mutation segregates with disease in known LVNC genes MYH7 and TPM1. Subsequent sequencing of MYH7 in a larger LVNC cohort identified 7 novel likely disease causing variants. In the fifth family, we identified a frameshift mutation in NNT, a nuclear-encoded mitochondrial protein, not implicated previously in human cardiomyopathies. Resequencing of NNT in additional LVNC families identified a second likely pathogenic missense allele. Suppression of nnt in zebrafish caused early ventricular malformation and contractility defects, probably driven by altered cardiomyocyte proliferation. In vivo complementation studies showed that mutant human NNT failed to rescue nnt morpholino-induced heart dysfunction, indicating a probable haploinsufficiency mechanism.

conclusionsTogether, our data expand the genetic spectrum of LVNC and demonstrate how the intersection of whole exome sequence with in vivo functional studies can accelerate the identification of genes that drive human genetic disorders.

Indexed as

Frameshift MutationAnimalsAnimals, Genetically ModifiedEmbryo, NonmammalianExomeFamily HealthFemaleGenetic Complementation TestGenetic Predisposition to DiseaseHumansIsolated Noncompaction of the Ventricular MyocardiumLuminescent ProteinsMaleMicroscopy, ConfocalMitochondrial ProteinsNADP Transhydrogenase, AB-SpecificLuminescent ProteinsMitochondrial ProteinsNADP Transhydrogenase, AB-SpecificNNT protein, humangeneticsgenomicshumanmutationnonisolated left ventricular noncompaction

Identifiers

PMID26025024
PMCPMC4545476
OpenAlexW2117701877

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.