April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
A Molecular Screening Test for Usher Syndrome
Author Affiliations & Notes
  • W. J. Kimberling
    Genetics, Boys Town Natl Research Hosp, Omaha, Nebraska
    Ophthalmology and Visual Sciences,
    University of Iowa Carver School of Medicine, Iowa City, Iowa
  • R. J. Smith
    Otolaryngology and Head and Neck Surgery,
    University of Iowa Carver School of Medicine, Iowa City, Iowa
  • A. V. Drack
    Ophthalmology and Visual Sciences,
    University of Iowa Carver School of Medicine, Iowa City, Iowa
  • E. M. Stone
    Ophthalmology and Visual Sciences,
    Howard Hughes Medical Institute,
    University of Iowa Carver School of Medicine, Iowa City, Iowa
  • G. A. Fishman
    Ophthalmology, University of Illinois Medical School, Chicago, Illinois
  • S. G. Jacobson
    Scheie Eye Institute, Philadelphia, Pennsylvania
  • R. G. Weleber
    Casey Eye Institute, Oregon Health & Science University, Portland, Oregon
  • L. M. Streb
    Ophthalmology and Visual Sciences,
    University of Iowa Carver School of Medicine, Iowa City, Iowa
  • Footnotes
    Commercial Relationships  W.J. Kimberling, None; R.J. Smith, None; A.V. Drack, None; E.M. Stone, None; G.A. Fishman, None; S.G. Jacobson, None; R.G. Weleber, None; L.M. Streb, None.
  • Footnotes
    Support  HHMI; FFB 0606-0343 and Center Grants; NIH DC003544; Hear See Hope Grant; Research to Prevent Blindness grant
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2308. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      W. J. Kimberling, R. J. Smith, A. V. Drack, E. M. Stone, G. A. Fishman, S. G. Jacobson, R. G. Weleber, L. M. Streb; A Molecular Screening Test for Usher Syndrome. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2308.

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Usher syndrome (US) is the main cause of combined deaf/blindness in the world. Early diagnosis of Usher syndrome promises benefits for early rehabilitation, education and family planning, and provides the basis for natural history studies. However, current approaches for screening children are expensive and have limited sensitivity. An inexpensive DNA based screening to detect US in high risk children is urgently needed.

Methods: : The screening test was developed using the Applied Biosystems SNPlexTM platform and is directed against 95 recurring mutations observed in the Usher genes. Specificity of the test was determined using controls with the known mutations. Sensitivity was determined in 250 subjects across three phenotypic groups: hearing impaired with RP, ARRP alone, and hearing loss alone.

Results: : Specificity was determined to be 93%. The sensitivity was 98%. The theoretical detection rate was estimated to be 52% but the observed detection rate was 42%. The detection rate varied depending upon the phenotype of the subject referred for testing.

Conclusions: : Newborn hearing screening programs now routinely identify very young children at high risk for US. The integration of US testing and tests for other genetic causes of hearing loss into newborn hearing screening programs has great potential to benefit Usher patients and their families. However, a major obstacle to US screening has been cost. This DNA screening test effectively addresses that issue. Other costs associated with screening will need to be also considered: positive results require follow up to confirm the existence and phase of mutations by conventional DNA sequencing; clinical testing of retinal function is required to confirm the diagnosis at the phenotypic level. This tiered approach reduces the cost of screening to a manageable level making possible large scale screening projects to detect US children at the earliest stages of their RP. In addition to providing useful information to caregivers and educators of the deaf and hard of hearing, screening programs could provide subjects suitable for natural history studies to identify differences in the early development of RP on a genotype specific basis.

Keywords: gene screening • clinical (human) or epidemiologic studies: systems/equipment/techniques • retina 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.