Original articleWhole-Exome Sequencing Identifies Biallelic IDH3A Variants as a Cause of Retinitis Pigmentosa Accompanied by Pseudocoloboma
Section snippets
Participants and Clinical Evaluation
The study protocol adhered to the tenets of the Declaration of Helsinki and received approval from the respective local ethics committees. Written informed consent was obtained from all participants or parents of children before their inclusion in this study. Patients were ascertained in the Rotterdam Eye Hospital (Rotterdam, The Netherlands), Hadassah-Hebrew University Medical Center (Jerusalem, Israel), or Leiden University Medical Center (Leiden, The Netherlands), or were recruited from the
Clinical Findings
We ascertained 7 patients from 4 families between the ages of 3 and 26 years. Their clinical characteristics are summarized in Table 1, and the family pedigrees are shown in Figure 1. All patients had early-onset night blindness and were diagnosed between 1 and 11 years of age. Visual acuity (VA) was available for all patients and ranged from 20/20 to counting fingers at 1 m.
The youngest patient (patient A-II:2) of a Dutch family was diagnosed with a macular pseudocoloboma at the age of 1 year
Discussion
In this study, we identified novel variants in IDH3A in 4 patients with typical arRP and 3 patients with arRP and macular pseudocoloboma from 4 unrelated families. These families originated from The Netherlands, Israel, and South Africa. All patients showed visual symptoms early in life, ranging from night blindness to severe visual impairment. In patients with RP and macular pseudocoloboma (patients A-II:2, D-II:2, and D-II:3), the visual impairment was more severe than in patients with
Acknowledgments
The authors thank the patients and their family members for their participation.
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Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Supported by the Foundation Combined Ophthalmic Research Rotterdam (CORR), Rotterdam, The Netherlands (to L.H.M.P); the Directorate General for Higher Education (DIKTI) of the Ministry for National Education of Indonesia and the Radboud University Medical Center, Nijmegen, The Netherlands (to G.D.N.A.); Retina South Africa, South Africa; the South African Medical Research Council, Cape Town, South Africa; the National Research Foundation of South Africa, Pretoria, South Africa; the United States–Israel Binational Science Foundation, Jerusalem, Israel (grant no.: 2011202 [to D.S., A.S.]); Foundation Fighting Blindness, Columbia, Maryland (grant no.: BR-GE-0214-0639 [to D.S., E.M.H.F.B.]); a Yedidut Research Grant, Mexico City, Mexico, [to E.M.F.H.B.]; and the Intramural Research Program of the National Eye Institute, National Institutes of Health, Bethesda, Maryland (grant no.: EY000546).
Author Contributions:
Conception and design: Ramesar, Swaroop, Sharon, Cremers
Analysis and interpretation: Pierrache, Kimchi, Ratnapriya, Roberts, Astuti, Beryozkin, Bongers, Ramesar, Swaroop, van den Born, Sharon, Cremers
Data collection: Pierrache, Kimchi, Ratnapriya, Roberts, Astuti, Obolensky, Tjon-Fo-Sang, Schuil, Beryozkin, Klaver, Bongers, Haer-Wigman, Schalij, Breuning, Fischer, Banin, van den Born
Obtained funding: none
Overall responsibility: Pierrache, Kimchi, Ratnapriya, Roberts, Astuti, Obolensky, Tjon-Fo-Sang, Schuil, Beryozkin, Klaver, Bongers, Haer-Wigman, Schalij, Breuning, Fischer, Banin, Ramesar, Swaroop, van den Born, Sharon, Cremers
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Laurence H.M. Pierrache, MD, MSc, Adva Kimchi, MSc, Rinki Ratnapriya, PhD, and Lisa Roberts, MSc contributed equally as first authors.
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Eyal Banin, MD, PhD, Raj S. Ramesar, PhD, MSc, Anand Swaroop, PhD, L. Ingeborgh van den Born, MD, PhD, Dror Sharon, PhD, and Frans P.M. Cremers, PhD share senior authorship.