Steun ons werk
Decorative header background

Macular Dystrophy and Cone-Rod Dystrophy Caused by Mutations in the RP1 Gene

Publicatiejaar 2019
Gepubliceerd in Investigative Ophthalmology & Visual Science
Auteur(s) Sanne K Verbakel, Ramon A C van Huet, Anneke I den Hollander, Maartje J Geerlings, Eveline Kersten, B Jeroen Klevering, Caroline C W Klaver, A.S. Plomp, Nieneke L Wesseling, A.A.B. Bergen, Konstantinos Nikopoulos, Carlo Rivolta, Yasuhiro Ikeda, Koh-Hei Sonoda, Yuko Wada, Camiel J F Boon, Toru Nakazawa, Carel B Hoyng, Koji M Nishiguchi

Purpose: To describe the clinical and genetic spectrum of RP1-associated retinal dystrophies.

Methods: In this multicenter case series, we included 22 patients with RP1-associated retinal dystrophies from 19 families from The Netherlands and Japan. Data on clinical characteristics, visual acuity, visual field, ERG, and retinal imaging were extracted from medical records over a mean follow-up of 8.1 years.

Results: Eleven patients were diagnosed with autosomal recessive macular dystrophy (arMD) or autosomal recessive cone-rod dystrophy (arCRD), five with autosomal recessive retinitis pigmentosa (arRP), and six with autosomal dominant RP (adRP). The mean age of onset was 40.3 years (range 14-56) in the patients with arMD/arCRD, 26.2 years (range 18-40) in adRP, and 8.8 years (range 5-12) in arRP patients. All patients with arMD/arCRD carried either the hypomorphic p.Arg1933* variant positioned close to the C-terminus (8 of 11 patients) or a missense variant in exon 2 (3 of 11 patients), compound heterozygous with a likely deleterious frameshift or nonsense mutation, or the p.Gln1916* variant. In contrast, all mutations identified in adRP and arRP patients were frameshift and/or nonsense variants located far from the C-terminus.

Conclusions: Mutations in the RP1 gene are associated with a broad spectrum of progressive retinal dystrophies. In addition to adRP and arRP, our study provides further evidence that arCRD and arMD are RP1-associated phenotypes as well. The macular involvement in patients with the hypomorphic RP1 variant suggests that macular function may remain compromised if expression levels of RP1 do not reach adequate levels after gene augmentation therapy.

Steun ons werk

De Stichting Vrienden van het Herseninstituut ondersteunt baanbrekend hersenonderzoek. U kunt ons daarbij helpen.

Steun ons werk

Wij, hersenonderzoekers, willen het brein nog beter begrijpen en zo doorbraken realiseren in de behandeling van ziektes als MS, Parkinson, Alzheimer en depressie. Om onze missie te volbrengen, willen wij ons volledig concentreren op ons onderzoek. Wil je ons daarbij helpen?

Doe een donatie of  schrijf je in voor onze nieuwsbrief!

Hartelijk dank!