Retinal disease course in Usher syndrome 1B due to MYO7A mutations

Samuel G. Jacobson, Artur V. Cideciyan, Dan Gibbs, Alexander Sumaroka, Alejandro J. Roman, Tomas S. Aleman, Sharon B. Schwartz, Melani B. Olivares, Robert C. Russell, Janet D. Steinberg, Margaret A. Kenna, William J. Kimberling, Heidi L. Rehm, David S. Williams

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Purpose. To determine the disease course in Usher syndrome type IB (USH1B) caused by myosin 7A (MYO7A) gene mutations. Methods. USH1B patients (n = 33, ages 2-61) representing 25 different families were studied by ocular examination, kinetic and chromatic static perimetry, dark adaptometry, and optical coherence tomography (OCT). Consequences of the mutant alleles were predicted. Results. All MYO7A patients had severely abnormal ERGs, but kinetic fields revealed regional patterns of visual loss that suggested a disease sequence. Rod-mediated vision could be lost to different degrees in the first decades of life. Cone vision followed a more predictable and slower decline. Central vision ranged from normal to reduced in the first four decades of life and thereafter was severely abnormal. Dark adaptation kinetics was normal. Photoreceptor layer thickness in a wide region of central retina could differ dramatically between patients of comparable ages; and there were examples of severe losses in childhood as well as relative preservation in patients in the third decade of life. Comparisons were made between the mutant alleles in mild versus more severe phenotypes. Conclusions. A disease sequence in USH1B leads from generally full but impaired visual fields to residual small central islands. At most disease stages, there was preserved temporal peripheral field, a potential target for early phase clinical trials of gene therapy. From data comparing patients' rod disease in this cohort, the authors speculate that null MYO7A alleles could be associated with milder dysfunction and fewer photoreceptor structural losses at ages when other genotypes show more severe phenotypes.

Original languageEnglish (US)
Pages (from-to)7924-7936
Number of pages13
JournalInvestigative Ophthalmology and Visual Science
Volume52
Issue number11
DOIs
StatePublished - Oct 1 2011
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Retinal disease course in Usher syndrome 1B due to MYO7A mutations'. Together they form a unique fingerprint.

  • Cite this

    Jacobson, S. G., Cideciyan, A. V., Gibbs, D., Sumaroka, A., Roman, A. J., Aleman, T. S., Schwartz, S. B., Olivares, M. B., Russell, R. C., Steinberg, J. D., Kenna, M. A., Kimberling, W. J., Rehm, H. L., & Williams, D. S. (2011). Retinal disease course in Usher syndrome 1B due to MYO7A mutations. Investigative Ophthalmology and Visual Science, 52(11), 7924-7936. https://doi.org/10.1167/iovs.11-8313