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Transl Vis Sci Technol. 2019 Aug 19;8(4):24. doi: 10.1167/tvst.8.4.24. eCollection 2019 Jul.

Long-Term Follow-Up of Retinal Degenerations Associated With LRAT Mutations and Their Comparability to Phenotypes Associated With RPE65 Mutations.

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Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands.
Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands.
Bartiméus, Diagnostic Center for Complex Visual Disorders, Zeist, the Netherlands.
Department of Ophthalmology, Ghent University and Ghent University Hospital, Ghent, Belgium.
Center for Medical Genetics, Ghent University and Ghent University Hospital, Ghent, Belgium.
Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands.
Ophthalmic Genetics & Visual Electrophysiology, Division of Ophthalmology, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
The Netherlands Institute for Neuroscience (NIN-KNAW), Amsterdam, the Netherlands.



To investigate the natural history in patients with LRAT-associated retinal degenerations (RDs), in the advent of clinical trials testing treatment options.


A retrospective cohort of 13 patients with LRAT-RDs.


Twelve patients from a genetic isolate carried a homozygous c.12del mutation. One unrelated patient carried a homozygous c.326G>T mutation. The mean follow-up time was 25.3 years (SD 15.2; range 4.8-53.5). The first symptom was nyctalopia (n = 11), central vision loss (n = 1), or light-gazing (n = 1), and was noticed in the first decade of life. Seven patients (54%) reached low vision (visual acuity < 20/67), four of whom reaching blindness (visual acuity < 20/400), respectively, at mean ages of 49.9 (SE 5.4) and 59.9 (SE 3.1) years. The fundus appearance was variable. Retinal white dots were seen in six patients (46%). Full-field electroretinograms (n = 11) were nondetectable (n = 2; ages 31-60), reduced in a nonspecified pattern (n = 2; ages 11-54), or showed rod-cone (n = 6; ages 38-48) or cone-rod (n = 1; age 29) dysfunction. Optical coherence tomography (n = 4) showed retinal thinning but relative preservation of the (para-)foveal outer retinal layers in the second (n = 1) and sixth decade of life (n = 2), and profound chorioretinal degeneration from the eighth decade of life (n = 1).


LRAT-associated phenotypes in this cohort were variable and unusual, but generally milder than those seen in RPE65-associated disease, and may be particularly amenable to treatment. The window of therapeutic opportunity can be extended in patients with a mild phenotype.

Translational Relevance:

Knowledge of the natural history of LRAT-RDs is essential in determining the window of opportunity in ongoing and future clinical trials for novel therapeutic options.


cone-rod degeneration; disease progression; genetic diseases; retinitis pigmentosa

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