title: Retinal disease course in Usher syndrome 1B due to MYO7A mutations.
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.
authors.affiliation: Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, USA. jacobsos@mail.med.upenn.edu
authors.forename: Samuel G
authors.initials: SG
authors.lastname: Jacobson
authors.forename: Artur V
authors.initials: AV
authors.lastname: Cideciyan
authors.forename: Dan
authors.initials: D
authors.lastname: Gibbs
authors.forename: Alexander
authors.initials: A
authors.lastname: Sumaroka
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Roman
authors.forename: Tomas S
authors.initials: TS
authors.lastname: Aleman
authors.forename: Sharon B
authors.initials: SB
authors.lastname: Schwartz
authors.forename: Melani B
authors.initials: MB
authors.lastname: Olivares
authors.forename: Robert C
authors.initials: RC
authors.lastname: Russell
authors.forename: Janet D
authors.initials: JD
authors.lastname: Steinberg
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Kenna
authors.forename: William J
authors.initials: WJ
authors.lastname: Kimberling
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Rehm
authors.forename: David S
authors.initials: DS
authors.lastname: Williams
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003623:Dark Adaptation; D004596:Electroretinography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics*; D010641:Phenotype; D020419:Photoreceptor Cells, Vertebrate / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics / Q000503:physiopathology*; D041623:Tomography, Optical Coherence; D052245:Usher Syndromes / Q000235:genetics / Q000503:physiopathology*; D014786:Vision Disorders / Q000235:genetics / Q000503:physiopathology*; D058609:Visual Field Tests; D014794:Visual Fields / Q000502:physiology*; D055815:Young Adult
chemical_list: C000631455:MYO7A protein, human; D000081412:Myosin VIIa; D009218:Myosins