Exome sequences versus sequential gene testing in the UK highly specialised Service for Limb Girdle Muscular Dystrophy View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-09-06

AUTHORS

Elizabeth Harris, Ana Topf, Rita Barresi, Judith Hudson, Helen Powell, James Tellez, Debbie Hicks, Anna Porter, Marta Bertoli, Teresinha Evangelista, Chiara Marini-Betollo, Ólafur Magnússon, Monkol Lek, Daniel MacArthur, Kate Bushby, Hanns Lochmüller, Volker Straub

ABSTRACT

BACKGROUND: Limb girdle muscular dystrophies are a group of rare and genetically heterogeneous diseases that share proximal weakness as a common feature; however they are often lacking very specific phenotypic features to allow an accurate differential diagnosis based on the clinical signs only, limiting the diagnostic rate using phenotype driven genetic testing. Next generation sequencing provides an opportunity to obtain molecular diagnoses for undiagnosed patients, as well as identifying novel genetic causes of muscle diseases. We performed whole exome sequencing (WES) on 104 affected individuals from 75 families in who standard gene by gene testing had not yielded a diagnosis. For comparison we also evaluated the diagnostic rate using sequential gene by gene testing for 91 affected individuals from 84 families over a 2 year period. RESULTS: Patients selected for WES had undergone more extensive prior testing than those undergoing standard genetic testing and on average had had 8 genes screened already. In this extensively investigated cohort WES identified the genetic diagnosis in 28 families (28/75, 37%), including the identification of the novel gene ZAK and two unpublished genes. WES of a single affected individual with sporadic disease yielded a diagnosis in 13/38 (34%) of cases. In comparison, conventional gene by gene testing provided a genetic diagnosis in 28/84 (33%) families. Titinopathies and collagen VI related dystrophy were the most frequent diagnoses made by WES. Reasons why mutations in known genes were not identified previously included atypical phenotypes, reassignment of pathogenicity of variants, and in one individual mosaicism for a COL6A1 mutation which was undetected by prior direct sequencing. CONCLUSION: WES was able to overcome many limitations of standard testing and achieved a higher rate of diagnosis than standard testing even in this cohort of extensively investigated patients. Earlier application of WES is therefore likely to yield an even higher diagnostic rate. We obtained a high diagnosis rate in simplex cases and therefore such individuals should be included in exome or genome sequencing projects. Disease due to somatic mosaicism may be increasingly recognised due to the increased sensitivity of next generation sequencing techniques to detect low level mosaicism. More... »

PAGES

151

References to SciGraph publications

  • 2017-04-17. A window into living with an undiagnosed disease: illness narratives from the Undiagnosed Diseases Network in ORPHANET JOURNAL OF RARE DISEASES
  • 2014-03-20. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine in TRIALS
  • 2013-06-20. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing in GENETICS IN MEDICINE
  • 2015-02-25. Next generation sequencing in sporadic retinoblastoma patients reveals somatic mosaicism in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 2014-11-13. The cost-effectiveness of returning incidental findings from next-generation genomic sequencing in GENETICS IN MEDICINE
  • 2017-07-06. Affected female carriers of MTM1 mutations display a wide spectrum of clinical and pathological involvement: delineating diagnostic clues in ACTA NEUROPATHOLOGICA
  • 2011-06-24. From proteins to genes: immunoanalysis in the diagnosis of muscular dystrophies in SKELETAL MUSCLE
  • 2016-10-06. The sensitivity of exome sequencing in identifying pathogenic mutations for LGMD in the United States in JOURNAL OF HUMAN GENETICS
  • 2014-04-23. Guidelines for investigating causality of sequence variants in human disease in NATURE
  • 2016-01-25. Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing in ORPHANET JOURNAL OF RARE DISEASES
  • <error retrieving object. in <ERROR RETRIEVING OBJECT
  • 2015-01-28. A mixed methods study of age at diagnosis and diagnostic odyssey for Duchenne muscular dystrophy in EUROPEAN JOURNAL OF HUMAN GENETICS
  • 2016-09-27. A first-line diagnostic assay for limb-girdle muscular dystrophy and other myopathies in HUMAN GENOMICS
  • 2015-10-19. Unrevealed mosaicism in the next-generation sequencing era in MOLECULAR GENETICS AND GENOMICS
  • 2016-02-17. Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy in JOURNAL OF NEUROLOGY
  • 2016-04-01. Limb-girdle muscular dystrophies — international collaborations for translational research in NATURE REVIEWS NEUROLOGY
  • 2016-06-30. Target resequencing of neuromuscular disease-related genes using next-generation sequencing for patients with undiagnosed early-onset neuromuscular disorders in JOURNAL OF HUMAN GENETICS
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1186/s13023-017-0699-9

    DOI

    http://dx.doi.org/10.1186/s13023-017-0699-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1091499668

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28877744


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