Johannes Birtel1,2, Martin Gliem1,2, Elisabeth Mangold3, Lars Tebbe4, Isabel Spier3, Philipp L Müller1,2, Frank G Holz1,2, Christine Neuhaus5, Uwe Wolfrum4, Hanno J Bolz5,6, Peter Charbel Issa1,2,7. 1. Department of Ophthalmology, University of Bonn, Bonn, Germany. 2. Center for Rare Diseases Bonn, University of Bonn, Bonn, Germany. 3. Institute of Human Genetics, University of Bonn, Bonn, Germany. 4. Institute of Molecular Physiology and Molecular Cell Biology, Mainz, Germany. 5. Bioscientia Center for Human Genetics, Ingelheim, Germany. 6. Institute of Human Genetics, University of Cologne, Cologne, Germany. 7. Oxford Eye Hospital, Oxford University Hospitals NHS Foundation Trust, and the Nuffield Laboratory of Ophthalmology, Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom.
Abstract
Purpose: This study sought to characterize the ophthalmic and extraocular phenotype in patients with known and novel KIF11 mutations. Methods: Four patients (3, 5, 36, and 38 years of age, on father-daughter constellation) from three unrelated families were characterized by retinal examination including multimodal retinal imaging, investigation for syndromic disease manifestations, and targeted next-generation sequencing. The subcellular localization of Kif11 in the retina was analyzed by light and electron microcopy. Results: There was considerable interindividual and intrafamilial phenotypic heterogeneity of KIF11-related retinopathy. Two patients presented with a progressive retinal dystrophy, one with chorioretinal dysplasia and one with familial exudative vitreoretinopathy (FEVR) in one eye and thinning of the photoreceptor layer in the fellow eye. Obvious syndromic disease manifestations were present only in the youngest patient, but minor signs (e.g. reduced head circumference) were present in the three other individuals. Immunohistochemistry results demonstrated Kif11 localization in the inner segment and ciliary compartments of photoreceptor cells and in the retinal pigment epithelium. Conclusions: Progressive retinal degeneration in KIF11-related retinopathy indicates a role for 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 retinopathy which may overlap. KIF11 should be considered in the screening of patients with retinal dystrophies because other syndromic manifestations may be subtle. Evaluation of head circumference may be considered as a potential shortcut to the genetic diagnosis. The localization of Kif11 in photoreceptor cells indicates a retinal ciliopathy.
Purpose: This study sought to characterize the ophthalmic and extraocular phenotype in patients with known and novel KIF11 mutations. Methods: Four patients (3, 5, 36, and 38 years of age, on father-daughter constellation) from three unrelated families were characterized by retinal examination including multimodal retinal imaging, investigation for syndromic disease manifestations, and targeted next-generation sequencing. The subcellular localization of Kif11 in the retina was analyzed by light and electron microcopy. Results: There was considerable interindividual and intrafamilial phenotypic heterogeneity of KIF11-related retinopathy. Two patients presented with a progressive retinal dystrophy, one with chorioretinal dysplasia and one with familial exudative vitreoretinopathy (FEVR) in one eye and thinning of the photoreceptor layer in the fellow eye. Obvious syndromic disease manifestations were present only in the youngest patient, but minor signs (e.g. reduced head circumference) were present in the three other individuals. Immunohistochemistry results demonstrated Kif11 localization in the inner segment and ciliary compartments of photoreceptor cells and in the retinal pigment epithelium. Conclusions: Progressive retinal degeneration in KIF11-related retinopathy indicates a role for 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 retinopathy which may overlap. KIF11 should be considered in the screening of patients with retinal dystrophies because other syndromic manifestations may be subtle. Evaluation of head circumference may be considered as a potential shortcut to the genetic diagnosis. The localization of Kif11 in photoreceptor cells indicates a retinal ciliopathy.
Authors: Anna A Kiseleva; Vladislav A Korobeynikov; Anna S Nikonova; Peishan Zhang; Petr Makhov; Alexander Y Deneka; Margret B Einarson; Ilya G Serebriiskii; Hanqing Liu; Jeffrey R Peterson; Erica A Golemis Journal: Clin Cancer Res Date: 2019-03-13 Impact factor: 12.531
Authors: Johannes Birtel; Tobias Eisenberger; Martin Gliem; Philipp L Müller; Philipp Herrmann; Christian Betz; Diana Zahnleiter; Christine Neuhaus; Steffen Lenzner; Frank G Holz; Elisabeth Mangold; Hanno J Bolz; Peter Charbel Issa Journal: Sci Rep Date: 2018-03-19 Impact factor: 4.379