Evidence map›Paper›PMID 24706943›Full record

ArticleJournal of neurology, neurosurgery, and psychiatry2014

Whole-genome sequencing and the clinician: a tale of two cities.

A Reghan Foley, Robert D S Pitceathly, Jie He, Jihee Kim, Nathaniel M Pearson, Francesco Muntoni, Michael G Hanna

Abstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of neurology, neurosurgery, and psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

7 authors.

A Reghan FoleyDubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
Robert D S PitceathlyMRC Centre for Neuromuscular Diseases, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.
Jie HeKnome, Inc., Cambridge, Massachusetts, USA Foundation Medicine, Inc., Cambridge, Massachusetts, USA.
Jihee KimDepartment of Comparative Biomedical Sciences, Royal Veterinary College, London, UK.
Nathaniel M PearsonKnome, Inc., Cambridge, Massachusetts, USA Ingenuity Systems/QIAGEN, Redwood City, California, USA.
Francesco MuntoniDubowitz Neuromuscular Centre, MRC Centre for Neuromuscular Diseases, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK.
Michael G HannaMRC Centre for Neuromuscular Diseases, University College London Institute of Neurology and National Hospital for Neurology and Neurosurgery, London, UK.

Funding

Medical Research Council G0700718Medical Research Council G0800674Medical Research Council MR/K000608/1
6 · The paper itself

Abstract

backgroundClinicians are faced with unprecedented opportunities to identify the genetic aetiologies of hitherto molecularly uncharacterised conditions via the use of high-throughput sequencing. Access to genomic technology and resultant data is no longer limited to clinicians, geneticists and bioinformaticians, however; ongoing commercialisation gives patients themselves ever greater access to sequencing services. We report an increasingly common medical scenario by describing two neuromuscular patients--a mother and adult son--whose consumer access to whole-genome sequencing affected their diagnostic journey.

resultsWhole-genome sequencing initiated by the patients--to predict their risk of common diseases--revealed that they share several variants potentially relevant to neuromuscular diseases, which initially sidetracked diagnostic efforts. Since eventual clinical reassessment, including muscle imaging, pointed towards Bethlem myopathy, a collagen VI-related myopathy, we pursued Sanger sequencing of COL6A1, COL6A2 and COL6A3. This targeted approach revealed a heterozygous causative variant in COL6A3 (c.6365G>T (p.Gly2122Val)), shared by both individuals, that was not flagged by the interpretation of the whole-genome sequencing data.

conclusionsThis report highlights the essential interplay of clinical and genomic expertise in realising the potential of high-throughput sequencing. In an era when patients themselves may bring their own data to the table, definitively identifying clinically significant genomic variants will require close collaboration among clinicians, geneticists and bioinformaticians.

Indexed as

Precision MedicineAdultCollagen Type VIContractureFemaleGenetic Predisposition to DiseaseGenetics, MedicalGenome, HumanHigh-Throughput Nucleotide SequencingHumansMagnetic Resonance ImagingMaleMuscular DystrophiesNeuromuscular DiseasesCollagen Type VICOLLAGENGENETICSMYOPATHY

Identifiers

PMID24706943
PMCPMC4145416

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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.