Whole exome sequencing is an efficient, sensitive and specific method for determining the genetic cause of short-rib thoracic dystrophies

A.M. Mcinerney-Leo, J.E. Harris, P.J. Leo, M.S. Marshall, B. Gardiner, E. Kinning, H.Y. Leong, Fiona Mckenzie, W.P. Ong, J. Vodopiutz, C. Wicking, M.A. Brown, A. Zankl, E.L. Duncan

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    24 Citations (Scopus)

    Abstract

    © 2014 John Wiley & Sons A/S. Short-rib thoracic dystrophies (SRTDs) are congenital disorders due to defects in primary cilium function. SRTDs are recessively inherited with mutations identified in 14 genes to date (comprising 398 exons). Conventional mutation detection (usually by iterative Sanger sequencing) is inefficient and expensive, and often not undertaken. Whole exome massive parallel sequencing has been used to identify new genes for SRTD (WDR34, WDR60 and IFT172); however, the clinical utility of whole exome sequencing (WES) has not been established. WES was performed in 11 individuals with SRTDs. Compound heterozygous or homozygous mutations were identified in six confirmed SRTD genes in 10 individuals (IFT172, DYNC2H1, TTC21B, WDR60, WDR34 and NEK1), giving overall sensitivity of 90.9%. WES data from 993 unaffected individuals sequenced using similar technology showed two individuals with rare (minor allele frequency 99%). Costs for consumables, laboratory processing and bioinformatic analysis were
    Original languageEnglish
    Pages (from-to)550-557
    JournalClinical Genetics
    Volume88
    Issue number6
    Early online date17 Feb 2015
    DOIs
    Publication statusPublished - Dec 2015

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