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. 2016 Nov;18(11):1090-1096.
doi: 10.1038/gim.2016.1. Epub 2016 Mar 3.

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders

Zornitza Stark  1 , Tiong Y Tan  1   2 , Belinda Chong  1 , Gemma R Brett  1   3 , Patrick Yap  1 , Maie Walsh  1 , Alison Yeung  1 , Heidi Peters  1   2   4 , Dylan Mordaunt  1   2   4 , Shannon Cowie  1 , David J Amor  1   2 , Ravi Savarirayan  1   2 , George McGillivray  1 , Lilian Downie  1 , Paul G Ekert  1   2 , Christiane Theda  1   2   5 , Paul A James  6 , Joy Yaplito-Lee  1   4 , Monique M Ryan  1   2   4 , Richard J Leventer  1   2   4 , Emma Creed  1   3   6 , Ivan Macciocca  1 , Katrina M Bell  1 , Alicia Oshlack  1   2 , Simon Sadedin  1 , Peter Georgeson  2 , Charlotte Anderson  2 , Natalie Thorne  1   2   3 , Melbourne Genomics Health Alliance, Clara Gaff  2   3 , Susan M White  1   2
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Free article

A prospective evaluation of whole-exome sequencing as a first-tier molecular test in infants with suspected monogenic disorders

Zornitza Stark et al. Genet Med. 2016 Nov.
Free article

Abstract

Purpose: To prospectively evaluate the diagnostic and clinical utility of singleton whole-exome sequencing (WES) as a first-tier test in infants with suspected monogenic disease.

Methods: Singleton WES was performed as a first-tier sequencing test in infants recruited from a single pediatric tertiary center. This occurred in parallel with standard investigations, including single- or multigene panel sequencing when clinically indicated. The diagnosis rate, clinical utility, and impact on management of singleton WES were evaluated.

Results: Of 80 enrolled infants, 46 received a molecular genetic diagnosis through singleton WES (57.5%) compared with 11 (13.75%) who underwent standard investigations in the same patient group. Clinical management changed following exome diagnosis in 15 of 46 diagnosed participants (32.6%). Twelve relatives received a genetic diagnosis following cascade testing, and 28 couples were identified as being at high risk of recurrence in future pregnancies.

Conclusions: This prospective study provides strong evidence for increased diagnostic and clinical utility of singleton WES as a first-tier sequencing test for infants with a suspected monogenic disorder. Singleton WES outperformed standard care in terms of diagnosis rate and the benefits of a diagnosis, namely, impact on management of the child and clarification of reproductive risks for the extended family in a timely manner.Genet Med 18 11, 1090-1096.

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References

    1. Sci Transl Med. 2012 Oct 3;4(154):154ra135 - PubMed
    1. Hum Mutat. 2013 Dec;34(12):1721-6 - PubMed
    1. Sci Transl Med. 2014 Dec 3;6(265):265ra168 - PubMed
    1. Am J Hum Genet. 2014 Jun 5;94(6):809-17 - PubMed
    1. Nat Genet. 2003 Mar;33(3):388-91 - PubMed

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