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Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy

The aim of the study was to determine the rate of retinal degeneration in patients with c.2610C>A (p.Cys870*) in USH2A exon 13, amenable to exon skipping therapy. There were nine patients from seven families, three of whom were male (two were homozygous). Seven patients had follow-up data (median...

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Autores principales: Čadonič, Katja, Sajovic, Jana, Hawlina, Marko, Fakin, Ana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048357/
https://www.ncbi.nlm.nih.gov/pubmed/36980924
http://dx.doi.org/10.3390/genes14030652
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author Čadonič, Katja
Sajovic, Jana
Hawlina, Marko
Fakin, Ana
author_facet Čadonič, Katja
Sajovic, Jana
Hawlina, Marko
Fakin, Ana
author_sort Čadonič, Katja
collection PubMed
description The aim of the study was to determine the rate of retinal degeneration in patients with c.2610C>A (p.Cys870*) in USH2A exon 13, amenable to exon skipping therapy. There were nine patients from seven families, three of whom were male (two were homozygous). Seven patients had follow-up data (median of 11 years). Analysis included best corrected visual acuity (BCVA, decimal Snellen), visual field (Goldmann perimetry target II/4), fundus autofluorescence (FAF), optical coherence tomography (OCT), and microperimetry (MP). The median age at the onset of nyctalopia was 20 years (range, 8–35 years of age). At the first exam, at a median age of 42 years, the median BCVA was 0.5 (0.2–1.0), and the median visual field diameter was 23° (5°–114°). Imaging showed a hyperautofluorescent ring delineating preserved foveal photoreceptors in 78% (7/9) of patients, while 22% (2/9) had a hyperautofluorescent patch or atrophy, reflecting advanced disease. Survival analysis predicted that 50% of patients reach legal blindness based on a visual field diameter < 20° at the age of 52 (95% CI, 45–59) and legal blindness based on a BCVA ≤ 0. 1 (20/200) at the age of 55 (95% CI, 46–66). Visual field constriction occurred at the median rate of radial 1.5 deg/year, and hyperautofluorescent ring constriction occurred at the median rate of 34 μm/year. A non-null second allele was found in two patients: p.Thr4315Pro and p.Arg303His; the patient with p.Arg303His had a milder disease. The rates of progression will be useful in the design and execution of clinical trials.
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spelling pubmed-100483572023-03-29 Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy Čadonič, Katja Sajovic, Jana Hawlina, Marko Fakin, Ana Genes (Basel) Article The aim of the study was to determine the rate of retinal degeneration in patients with c.2610C>A (p.Cys870*) in USH2A exon 13, amenable to exon skipping therapy. There were nine patients from seven families, three of whom were male (two were homozygous). Seven patients had follow-up data (median of 11 years). Analysis included best corrected visual acuity (BCVA, decimal Snellen), visual field (Goldmann perimetry target II/4), fundus autofluorescence (FAF), optical coherence tomography (OCT), and microperimetry (MP). The median age at the onset of nyctalopia was 20 years (range, 8–35 years of age). At the first exam, at a median age of 42 years, the median BCVA was 0.5 (0.2–1.0), and the median visual field diameter was 23° (5°–114°). Imaging showed a hyperautofluorescent ring delineating preserved foveal photoreceptors in 78% (7/9) of patients, while 22% (2/9) had a hyperautofluorescent patch or atrophy, reflecting advanced disease. Survival analysis predicted that 50% of patients reach legal blindness based on a visual field diameter < 20° at the age of 52 (95% CI, 45–59) and legal blindness based on a BCVA ≤ 0. 1 (20/200) at the age of 55 (95% CI, 46–66). Visual field constriction occurred at the median rate of radial 1.5 deg/year, and hyperautofluorescent ring constriction occurred at the median rate of 34 μm/year. A non-null second allele was found in two patients: p.Thr4315Pro and p.Arg303His; the patient with p.Arg303His had a milder disease. The rates of progression will be useful in the design and execution of clinical trials. MDPI 2023-03-05 /pmc/articles/PMC10048357/ /pubmed/36980924 http://dx.doi.org/10.3390/genes14030652 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Čadonič, Katja
Sajovic, Jana
Hawlina, Marko
Fakin, Ana
Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy
title Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy
title_full Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy
title_fullStr Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy
title_full_unstemmed Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy
title_short Natural Disease Course in Usher Syndrome Patients Harboring USH2A Variant p.Cys870* in Exon 13, Amenable to Exon Skipping Therapy
title_sort natural disease course in usher syndrome patients harboring ush2a variant p.cys870* in exon 13, amenable to exon skipping therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10048357/
https://www.ncbi.nlm.nih.gov/pubmed/36980924
http://dx.doi.org/10.3390/genes14030652
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