Retinal Disease in Usher Syndrome III Caused by Mutations in the Clarin-1 Gene

¹ Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, United States
² Department of Ophthalmology, Hebrew University-Hadassah Medical School, Jerusalem, Israel
³ Department of Genetics and the Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel
⁴ Howard Hughes Medical Institute and Department of Ophthalmology, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
⁵ Department of Otolaryngology, University of Miami, Miami, Florida, United States
⁶ Department of Genetics, Usher Syndrome Center, Boys Town National Research Hospital, Omaha, Nebraska, United States

^* To whom correspondence should be addressed. E-mail: jacobsos{at}mail.med.upenn.edu.

	Abstract

PURPOSE. To determine the retinal phenotype of Usher syndrome type III (USH3A) caused by clarin-1 (CLRN1) gene mutations in a non-Finnish population. METHODS. USH3A patients (n=13, ages 24-69) representing 11 different families were studied and results compared with those of USH2A (n=24, ages 17-66). Patients were evaluated by ocular examination, kinetic and static perimetry, near-infrared autofluorescence and optical coherence tomography (OCT). RESULTS. Ten of 11 families had Ashkenazi Jewish origins and the N48K CLRN1 mutation. Rod function was lost in the peripheral field in the first two decades of life but central rod function could be retained for another decade. Peripheral cone function was detectable into the third decade of life. Central cone function had a slower decline that extended for decades. Photoreceptor layer loss and features of retinal remodeling were present in retinal regions with severe visual dysfunction even at the youngest ages tested. Central retinal structure could be normal in younger patients but structural integrity was lost at increasing ages. RPE disease generally paralleled photoreceptor degeneration. Comparisons between USH3A and USH2A suggested a common rod and cone phenotype but a more accelerated time course of rod loss in USH3A. CONCLUSIONS. USH3A and USH2A share patterns of rod and cone dysfunction and retinal structural abnormalities. Based on peripheral function measurements, USH3A tended to be more rapidly progressive than USH2A.

Key Words: retinal degeneration, night vision, photoreceptor dystrophy, retinal dystrophy, retinitis pigmentosa, optical coherence tomography

This article has been cited by other articles:

				S. G. Jacobson, A. J. Roman, T. S. Aleman, A. Sumaroka, W. Herrera, E. A. M. Windsor, L. A. Atkinson, S. B. Schwartz, J. D. Steinberg, and A. V. Cideciyan Normal Central Retinal Function and Structure Preserved in Retinitis Pigmentosa Invest. Ophthalmol. Vis. Sci., February 1, 2010; 51(2): 1079 - 1085. [Abstract] [Full Text] [PDF]

				T. S. Aleman, N. Soumittra, A. V. Cideciyan, A. M. Sumaroka, V. L. Ramprasad, W. Herrera, E. A. M. Windsor, S. B. Schwartz, R. C. Russell, A. J. Roman, et al. CERKL Mutations Cause an Autosomal Recessive Cone-Rod Dystrophy with Inner Retinopathy Invest. Ophthalmol. Vis. Sci., December 1, 2009; 50(12): 5944 - 5954. [Abstract] [Full Text] [PDF]

				D. Gibbs, A. V. Cideciyan, S. G. Jacobson, and D. S. Williams Retinal Pigment Epithelium Defects in Humans and Mice with Mutations in MYO7A: Imaging Melanosome-Specific Autofluorescence Invest. Ophthalmol. Vis. Sci., September 1, 2009; 50(9): 4386 - 4393. [Abstract] [Full Text] [PDF]

				G. Tian, Y. Zhou, D. Hajkova, M. Miyagi, A. Dinculescu, W. W. Hauswirth, K. Palczewski, R. Geng, K. N. Alagramam, J. Isosomppi, et al. Clarin-1, Encoded by the Usher Syndrome III Causative Gene, Forms a Membranous Microdomain: POSSIBLE ROLE OF CLARIN-1 IN ORGANIZING THE ACTIN CYTOSKELETON J. Biol. Chem., July 10, 2009; 284(28): 18980 - 18993. [Abstract] [Full Text] [PDF]

				S. G. Jacobson, T. S. Aleman, A. Sumaroka, A. V. Cideciyan, A. J. Roman, E. A. M. Windsor, S. B. Schwartz, H. L. Rehm, and W. J. Kimberling Disease Boundaries in the Retina of Patients with Usher Syndrome Caused by MYO7A Gene Mutations Invest. Ophthalmol. Vis. Sci., April 1, 2009; 50(4): 1886 - 1894. [Abstract] [Full Text] [PDF]

				A. V. Cideciyan, M. Swider, T. S. Aleman, Y. Tsybovsky, S. B. Schwartz, E. A.M. Windsor, A. J. Roman, A. Sumaroka, J. D. Steinberg, S. G. Jacobson, et al. ABCA4 disease progression and a proposed strategy for gene therapy Hum. Mol. Genet., March 1, 2009; 18(5): 931 - 941. [Abstract] [Full Text] [PDF]