Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype

Sharon B. Schwartz, Tomas S. Aleman, Artur V. Cideciyan, Elizabeth A M Windsor, Alexander Sumaroka, Alejandro J. Roman, Tej Rane, Elaine E. Smilko, Jean Bennett, Edwin M. Stone, William J. Kimberling, Xue Z Liu, Samuel G. Jacobson

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Abstract

PURPOSE. To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome. METHODS. Three siblings with USH2C and 14 patients with USH2A were studied. Visual function was measured by kinetic perimetry, static chromatic perimetry, and electroretinography (ERG). Central retinal microstructure was studied with optical coherence tomography (OCT). RESULTS. The siblings with VLGR1 mutation showed abnormal photoreceptor-mediated function in all retinal regions, and there was greater rod than cone dysfunction. USH2A had a wider spectrum of disease expression and included patients with normal function in some retinal regions. When abnormalities were detected, there was more rod than cone dysfunction. Retinal microstructure in both USH2C and USH2A shared the abnormality of loss of outer nuclear layer thickness. Central retinal structure in both genotypes was complicated by cystic macular lesions. A coincidental finding in an USH2C patient was that oral intake of antihistamines was associated with temporary resolution of the macular cystic change. CONCLUSIONS. USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer. An orderly progression through disease stages was estimated from cross-sectional and limited longitudinal data. Intrafamilial and interfamilial variation in retinal severity in USH2A, however, suggests that genetic or nongenetic modifiers may be involved in the disease expression.

Original languageEnglish
Pages (from-to)734-743
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume46
Issue number2
DOIs
StatePublished - Feb 1 2005

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Usher Syndromes
Vertebrate Photoreceptor Cells
Visual Field Tests
Phenotype
Mutation
Siblings
Genes
Electroretinography
Retinal Diseases
Histamine Antagonists
Optical Coherence Tomography
Disease Progression
Color
Genotype

ASJC Scopus subject areas

  • Ophthalmology

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Schwartz, S. B., Aleman, T. S., Cideciyan, A. V., Windsor, E. A. M., Sumaroka, A., Roman, A. J., ... Jacobson, S. G. (2005). Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype. Investigative Ophthalmology and Visual Science, 46(2), 734-743. https://doi.org/10.1167/iovs.04-1136

Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype. / Schwartz, Sharon B.; Aleman, Tomas S.; Cideciyan, Artur V.; Windsor, Elizabeth A M; Sumaroka, Alexander; Roman, Alejandro J.; Rane, Tej; Smilko, Elaine E.; Bennett, Jean; Stone, Edwin M.; Kimberling, William J.; Liu, Xue Z; Jacobson, Samuel G.

In: Investigative Ophthalmology and Visual Science, Vol. 46, No. 2, 01.02.2005, p. 734-743.

Research output: Contribution to journalArticle

Schwartz, SB, Aleman, TS, Cideciyan, AV, Windsor, EAM, Sumaroka, A, Roman, AJ, Rane, T, Smilko, EE, Bennett, J, Stone, EM, Kimberling, WJ, Liu, XZ & Jacobson, SG 2005, 'Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype', Investigative Ophthalmology and Visual Science, vol. 46, no. 2, pp. 734-743. https://doi.org/10.1167/iovs.04-1136
Schwartz, Sharon B. ; Aleman, Tomas S. ; Cideciyan, Artur V. ; Windsor, Elizabeth A M ; Sumaroka, Alexander ; Roman, Alejandro J. ; Rane, Tej ; Smilko, Elaine E. ; Bennett, Jean ; Stone, Edwin M. ; Kimberling, William J. ; Liu, Xue Z ; Jacobson, Samuel G. / Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype. In: Investigative Ophthalmology and Visual Science. 2005 ; Vol. 46, No. 2. pp. 734-743.
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T1 - Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype

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AU - Aleman, Tomas S.

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AU - Windsor, Elizabeth A M

AU - Sumaroka, Alexander

AU - Roman, Alejandro J.

AU - Rane, Tej

AU - Smilko, Elaine E.

AU - Bennett, Jean

AU - Stone, Edwin M.

AU - Kimberling, William J.

AU - Liu, Xue Z

AU - Jacobson, Samuel G.

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N2 - PURPOSE. To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome. METHODS. Three siblings with USH2C and 14 patients with USH2A were studied. Visual function was measured by kinetic perimetry, static chromatic perimetry, and electroretinography (ERG). Central retinal microstructure was studied with optical coherence tomography (OCT). RESULTS. The siblings with VLGR1 mutation showed abnormal photoreceptor-mediated function in all retinal regions, and there was greater rod than cone dysfunction. USH2A had a wider spectrum of disease expression and included patients with normal function in some retinal regions. When abnormalities were detected, there was more rod than cone dysfunction. Retinal microstructure in both USH2C and USH2A shared the abnormality of loss of outer nuclear layer thickness. Central retinal structure in both genotypes was complicated by cystic macular lesions. A coincidental finding in an USH2C patient was that oral intake of antihistamines was associated with temporary resolution of the macular cystic change. CONCLUSIONS. USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer. An orderly progression through disease stages was estimated from cross-sectional and limited longitudinal data. Intrafamilial and interfamilial variation in retinal severity in USH2A, however, suggests that genetic or nongenetic modifiers may be involved in the disease expression.

AB - PURPOSE. To investigate the retinal disease expression in USH2C, the subtype of Usher syndrome type 2 recently shown to be caused by mutation in the VLGR1 gene, and compare results with those from USH2A, a more common cause of Usher syndrome. METHODS. Three siblings with USH2C and 14 patients with USH2A were studied. Visual function was measured by kinetic perimetry, static chromatic perimetry, and electroretinography (ERG). Central retinal microstructure was studied with optical coherence tomography (OCT). RESULTS. The siblings with VLGR1 mutation showed abnormal photoreceptor-mediated function in all retinal regions, and there was greater rod than cone dysfunction. USH2A had a wider spectrum of disease expression and included patients with normal function in some retinal regions. When abnormalities were detected, there was more rod than cone dysfunction. Retinal microstructure in both USH2C and USH2A shared the abnormality of loss of outer nuclear layer thickness. Central retinal structure in both genotypes was complicated by cystic macular lesions. A coincidental finding in an USH2C patient was that oral intake of antihistamines was associated with temporary resolution of the macular cystic change. CONCLUSIONS. USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer. An orderly progression through disease stages was estimated from cross-sectional and limited longitudinal data. Intrafamilial and interfamilial variation in retinal severity in USH2A, however, suggests that genetic or nongenetic modifiers may be involved in the disease expression.

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