Evidence map›Paper›PMID 25564561›Full record

ArticleJournal of medical genetics2015

The kinetochore protein, CENPF, is mutated in human ciliopathy and microcephaly phenotypes.

Aoife M Waters, Rowan Asfahani, Paula Carroll, Louise Bicknell, Francesco Lescai, Alison Bright, Estelle Chanudet, Anthony Brooks, Sonja Christou-Savina, Guled Osman and 23 more

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

Article in Journal of medical genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
8.4field-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

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 81 citations in OpenAlex.

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  17. CENPF promotes the proliferation of renal cell carcinomaTranslational andrology and urology · 2023
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

33 authors at 13 institutions in 3 countries.

Aoife M WatersInstitute of Child Health, University College London, London, UK Department of Nephrology, Great Ormond Street Hospital NHS Foundation Trust, London, UK.
Rowan AsfahaniInstitute of Child Health, University College London, London, UK.
Paula CarrollInstitute of Genetics & Molecular Medicine, Edinburgh, UK.
Louise BicknellInstitute of Genetics & Molecular Medicine, Edinburgh, UK.
Francesco LescaiInstitute of Child Health, University College London, London, UK.
Alison BrightUniversity of Massachusetts, Boston, USA.
Estelle ChanudetInstitute of Child Health, University College London, London, UK.
Anthony BrooksInstitute of Child Health, University College London, London, UK.
Sonja Christou-SavinaInstitute of Child Health, University College London, London, UK.
Guled OsmanInstitute of Child Health, University College London, London, UK.
Patrick WalshInstitute of Child Health, University College London, London, UK.
Chiara BacchelliInstitute of Child Health, University College London, London, UK.
Ariane ChapgierInstitute of Child Health, University College London, London, UK.
Bertrand VernayInstitute of Child Health, University College London, London, UK.
David M BaderDepartment of Cell and Developmental Biology, Vanderbilt University, USA.
Charu DeshpandeDepartment of Clinical Genetics, Evelina Children's Hospital, London, UK.
Mary O' SullivanInstitute of Child Health, University College London, London, UK.
Louise OcakaInstitute of Child Health, University College London, London, UK.
Horia StanescuCentre for Nephrology, Royal Free Hospital, University College London, London, UK.
Helen S StewartDepartment of Clinical Genetics, Oxford Radcliffe Hospitals NHS Trust, Churchill Hospital, Oxford, UK.
Friedhelm HildebrandtDepartment of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, USA.
Edgar OttoDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan, USA.
Colin A JohnsonDepartment of Pediatrics, Leeds Institute of Biomedical and Clinical Sciences, Leeds, UK.
Katarzyna SzymanskaDepartment of Pediatrics, Leeds Institute of Biomedical and Clinical Sciences, Leeds, UK.
Nicholas KatsanisCenter for Human Disease Modeling, Department of Cell Biology, Duke University Medical Center.
Erica DavisCenter for Human Disease Modeling, Department of Cell Biology, Duke University Medical Center.
Robert KletaCentre for Nephrology, Royal Free Hospital, University College London, London, UK.
Mike HubankInstitute of Child Health, University College London, London, UK.
Stephen DoxseyUniversity of Massachusetts, Boston, USA.
Andrew JacksonInstitute of Genetics & Molecular Medicine, Edinburgh, UK MRC Human Genetics, University of Edinburgh, Edinburgh, UK.
Elia StupkaInstitute of Child Health, University College London, London, UK.
Mark WineyMolecular, Ceullular, and Developmental Biology, University of Colorado at Boulder, Boulder, CO 80309, USA.
Philip L BealesInstitute of Child Health, University College London, London, UK.
University College London · GBMRC Institute of Genetics and Molecular Medicine · GBThe Royal Free Hospital · GBUniversity of Massachusetts Boston · USBoston Children's Hospital · USChurchill Hospital · GBDuke Medical Center · USDuke University Hospital · USEvelina London Children's Healthcare · GBInstitute of Molecular Genetics · RUUniversity of Colorado System · USUniversity of Michigan–Ann Arbor · USVanderbilt University · US

Funding

Molecular Genetics of BBSR01HD042601 · NICHD · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI DAVIS, ERICA ELLEN · 2003 to 2023
$8.2M
Genetic and Functional Studies of Human Ciliary SyndromesR01DK072301 · NIDDK · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI DAVIS, ERICA ELLEN · 2005 to 2022
$7.2M
Novel genetics, pathobiology & therapy of nephronophthisis-related ciliopathiesR01DK068306 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI HILDEBRANDT, FRIEDHELM · 2004 to 2022
$6.6M
REGULATION OF CARDIAC MYOCYTE DIFFERENTIATIONR01HL037675 · NHLBI · WEILL MEDICAL COLLEGE OF CORNELL UNIV · PI BADER, DAVID M · 1986 to 2017
$4.7M
The Role of Basa Bodies in Wnt SignalingR01DK075972 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI KATSANIS, NICHOLAS · 2007 to 2015
$3.1M
Medical Research Council G0802138Medical Research Council G0802138/1Medical Research Council MC_PC_U127580972Medical Research Council MR/K010654/1NHLBI NIH HHS R01 HL037675NICHD NIH HHS R01 HD042601NIDDK NIH HHS DK-06308NIDDK NIH HHS R01 DK068306NIDDK NIH HHS R01 DK072301NIDDK NIH HHS R01 DK075972Wellcome Trust
6 · The paper itself

Abstract

backgroundMutations in microtubule-regulating genes are associated with disorders of neuronal migration and microcephaly. Regulation of centriole length has been shown to underlie the pathogenesis of certain ciliopathy phenotypes. Using a next-generation sequencing approach, we identified mutations in a novel centriolar disease gene in a kindred with an embryonic lethal ciliopathy phenotype and in a patient with primary microcephaly. METHODS AND

resultsWhole exome sequencing data from a non-consanguineous Caucasian kindred exhibiting mid-gestation lethality and ciliopathic malformations revealed two novel non-synonymous variants in CENPF, a microtubule-regulating gene. All four affected fetuses showed segregation for two mutated alleles [IVS5-2A>C, predicted to abolish the consensus splice-acceptor site from exon 6; c.1744G>T, p.E582X]. In a second unrelated patient exhibiting microcephaly, we identified two CENPF mutations [c.1744G>T, p.E582X; c.8692 C>T, p.R2898X] by whole exome sequencing. We found that CENP-F colocalised with Ninein at the subdistal appendages of the mother centriole in mouse inner medullary collecting duct cells. Intraflagellar transport protein-88 (IFT-88) colocalised with CENP-F along the ciliary axonemes of renal epithelial cells in age-matched control human fetuses but did not in truncated cilia of mutant CENPF kidneys. Pairwise co-immunoprecipitation assays of mitotic and serum-starved HEKT293 cells confirmed that IFT88 precipitates with endogenous CENP-F.

conclusionsOur data identify CENPF as a new centriolar disease gene implicated in severe human ciliopathy and microcephaly related phenotypes. CENP-F has a novel putative function in ciliogenesis and cortical neurogenesis.

Indexed as

Genetics, MedicalAnimalsCentriolesChromosomal Proteins, Non-HistoneCiliaExomeFemaleFetusHEK293 CellsHigh-Throughput Nucleotide SequencingHumansMaleMiceMicrocephalyMicrofilament ProteinsMutationcentromere protein FChromosomal Proteins, Non-HistoneMicrofilament ProteinsCENPFCiliopathyClinical geneticsMicrocephalyMolecular genetics

Identifiers

PMID25564561
PMCPMC4345935
OpenAlexW2101230544

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Registered trials

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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.