Retinal Disease Course in Usher Syndrome 1B Due to MYO7A Mutations

Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA.
Investigative ophthalmology & visual science (Impact Factor: 3.4). 08/2011; 52(11):7924-36. DOI: 10.1167/iovs.11-8313
Source: PubMed


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.

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    • "However, like other retinal degenerations , disease severity varies between patients depending on the MYO7A mutation(s) they carry ( Jacobson et al., 2011). Many USH1B patients retain central retinal structure and function as well as islands of peripheral/temporal field until late stages of the disease ( Jacobson et al., 2011). Detailed analyses of patient genotype and phenotype will therefore be required to understand the safest/most effective temporal and spatial parameters for clinical application of this technology. "
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