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Johannes Birtel, Martin Gliem, Elisabeth Mangold, Lars Tebbe, Isabel Spier, Philipp Mueller, Frank G Holz, Christine Neuhaus, Uwe Wolfrum, Hanno J. Bolz, Peter Charbel Issa; Novel insights in KIF11-related retinopathy. Invest. Ophthalmol. Vis. Sci. 2017;58(8):2760.
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© ARVO (1962-2015); The Authors (2016-present)
Mutations in KIF11 have been associated with a rare autosomal dominant syndrome that includes microcephaly, lymphedema, and mental retardation. Patients frequently also present with retinal changes including chorioretinopathy and/or familial exudative vitreoretinopathy (FEVR). This study characterizes patients with known and novel KIF11 mutations who were detected based on their ophthalmological phenotype.
Targeted NGS identified the patients with KIF11-associated disease reported herein. Four patients (age: 3, 5, 36, 38 years), including one father-daughter constellation, from three unrelated families underwent ophthalmic clinical examination and imaging, including OCT, fundus autofluorescence imaging and fundus photography. To assess retinal function, BCVA and electroretinography were performed. Syndromic features were assessed and immunohistochemical staining was performed.
There was considerable inter-individual and intra-familial phenotypic variability of KIF11-related retinopathy. The 5 and 38 years-old patients presented with a peculiar cone rod dystrophy (CRD), the 3 years-old with chorioretinal dysplasia and the 36 years-old with a FEVR in one eye and thinning of the photoreceptor layer in the fellow eye. The 38 years-old patient with CRD had a history of slow deterioration of visual function. Longitudinal retinal imaging indicated disease progression. Obvious syndromic manifestations were only present in the youngest patient, but minor signs, such as a low head circumference, were present in the three other individuals. Immunohistochemical staining of neuronal retina demonstrated KIF11 localization in the inner segment and in the ciliary compartments of photoreceptor cells.
Progressive retinal degeneration in KIF11-related retinopathy indicates a role of KIF11 not only in ocular development, but also in maintaining retinal morphology and function. The remarkable variability of the ocular phenotype suggests four different types of KIF11-associated retinopathy which may also occur in combination. The lack of obvious syndromic features indicates that KIF11 should be included in genetic testing of patients with apparently non-syndromic retinal dystrophies. Evaluation of head circumference by the ophthalmologist should be considered in patients with suspected KIF11-related retinopathy as a shortcut to the genetic diagnosis. The localization of KIF11 protein in photoreceptor cells indicates a retinal ciliopathy.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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