Evidence map›Paper›PMID 26077881›Full record

ArticleNature communications2015

Mutations in DYNC2LI1 disrupt cilia function and cause short rib polydactyly syndrome.

S Paige Taylor, Tiago J Dantas, Ivan Duran, Sulin Wu, Ralph S Lachman, University of Washington Center for Mendelian Genomics Consortium, Stanley F Nelson, Daniel H Cohn, Richard B Vallee, Deborah Krakow

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

Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 1 pooled it
8.6field-weighted citation impact, top 2% 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

50 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Ttc30a affects tubulin modifications in a model for ciliary chondrodysplasia with polycystic kidney disease.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  18. Review
  19. Review
  20. 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

10 authors at 4 institutions in 1 country.

S Paige TaylorDepartment of Human Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA.
Tiago J DantasDepartment of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
Ivan DuranDepartment of Orthopaedic Surgery and Orthopaedic Institute for Children, University of California, Los Angeles, Los Angeles, California 90095, USA.
Sulin WuDepartment of Orthopaedic Surgery and Orthopaedic Institute for Children, University of California, Los Angeles, Los Angeles, California 90095, USA.
Ralph S LachmanInternational Skeletal Dysplasia Registry, University of California, Los Angeles, Los Angeles, California 90095, USA.
University of Washington Center for Mendelian Genomics Consortium
Stanley F Nelson1] Department of Human Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Pathology and Laboratory Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
Daniel H Cohn1] Department of Orthopaedic Surgery and Orthopaedic Institute for Children, University of California, Los Angeles, Los Angeles, California 90095, USA [2] International Skeletal Dysplasia Registry, University of California, Los Angeles, Los Angeles, California 90095, USA [3] Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, Los Angeles, California 90095, USA.
Richard B ValleeDepartment of Pathology and Cell Biology, Columbia University, New York, New York 10032, USA.
Deborah Krakow1] Department of Human Genetics, University of California, Los Angeles, Los Angeles, California 90095, USA [2] Department of Orthopaedic Surgery and Orthopaedic Institute for Children, University of California, Los Angeles, Los Angeles, California 90095, USA [3] International Skeletal Dysplasia Registry, University of California, Los Angeles, Los Angeles, California 90095, USA.
University of California, Los Angeles · USUniversity of Washington · USColumbia University · USOrthopaedic Institute for Children · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
UW Center for Mendelian GenomicsU54HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, NICKERSON, DEBORAH A · 2012 to 2015
$20.0M
UW Center for Mendelian GenomicsUM1HG006493 · NHGRI · UNIVERSITY OF WASHINGTON · PI BAMSHAD, MICHAEL JOSEPH, LEAL, SUZANNE M · 2016 to 2020
$15.3M
Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
UCLA Muscular Dystrophy Core CenterP30AR057230 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SPENCER, MELISSA JAN · 2009 to 2018
$6.2M
Motor Proteins in Brain DevelopmentR01HD040182 · NICHD · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI VALLEE, RICHARD BERT · 2000 to 2016
$4.9M
UCLA Clinical and Translational Science InstituteKL2TR000122 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$4.5M
Exome sequencing in the skeletal dysplasiasR01AR062651 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COHN, DANIEL H · 2013 to 2017
$1.7M
Mechanism of Action of DynactinR01GM102347 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI VALLEE, RICHARD BERT · 2012 to 2015
$1.7M
Unraveling the mechanisms of prenatal-onset disorders affecting the skeletonR01AR066124 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI KRAKOW, DEBORAH · 2014 to 2018
$1.7M
NCATS NIH HHS KL2 TR000122NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NHGRI NIH HHS 1U54 HG006493NHGRI NIH HHS T32 HG002536NHGRI NIH HHS U54 HG006493NHGRI NIH HHS UM1 HG006493NIAMS NIH HHS P30 AR057230NIAMS NIH HHS R01 AR062651NIAMS NIH HHS R01AR062651NIAMS NIH HHS R01 AR066124NICHD NIH HHS R01 HD040182NICHD NIH HHS R01 HD40182NIGMS NIH HHS R01 GM102347PHS HHS CJX1-443835-WS-29646
6 · The paper itself

Abstract

The short rib polydactyly syndromes (SRPSs) are a heterogeneous group of autosomal recessive, perinatal lethal skeletal disorders characterized primarily by short, horizontal ribs, short limbs and polydactyly. Mutations in several genes affecting intraflagellar transport (IFT) cause SRPS but they do not account for all cases. Here we identify an additional SRPS gene and further unravel the functional basis for IFT. We perform whole-exome sequencing and identify mutations in a new disease-producing gene, cytoplasmic dynein-2 light intermediate chain 1, DYNC2LI1, segregating with disease in three families. Using primary fibroblasts, we show that DYNC2LI1 is essential for dynein-2 complex stability and that mutations in DYNC2LI1 result in variable length, including hyperelongated, cilia, Hedgehog pathway impairment and ciliary IFT accumulations. The findings in this study expand our understanding of SRPS locus heterogeneity and demonstrate the importance of DYNC2LI1 in dynein-2 complex stability, cilium function, Hedgehog regulation and skeletogenesis.

Indexed as

Biological TransportCiliaCytoplasmic DyneinsCytoskeletonFemaleFibroblastsFlagellaHedgehog ProteinsHumansMaleMutationPedigreeShort Rib-Polydactyly SyndromeCytoplasmic DyneinsDYNC2LI1 protein, humanHedgehog Proteins

Identifiers

PMID26077881
PMCPMC4470332
OpenAlexW2260102155

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.