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Case Reports
. 2024 Feb;12(2):e2404.
doi: 10.1002/mgg3.2404.

Novel hemizygous single-nucleotide duplication in RPGR in a patient with retinal dystrophy and sensorineural hearing loss

Ryan J German  1   2 , Blake Vuocolo  1   2 , Liesbeth Vossaert  1   3 , Nichole Owen  1   3 , Richard A Lewis  1   4   5 , Lisa Saba  6 ; Texome Project; Michael F Wangler  1   2   7 , Sandesh Nagamani  1   4   7
Affiliations
Case Reports

Novel hemizygous single-nucleotide duplication in RPGR in a patient with retinal dystrophy and sensorineural hearing loss

Ryan J German et al. Mol Genet Genomic Med. 2024 Feb.

Abstract

Background: The RPGR gene has been associated with X-linked cone-rod dystrophy. This report describes a variant in RPGR detected with exome sequencing (ES). Genes like RPGR have not always been included in panel-based testing and thus genome-wide tests such as ES may be required for accurate diagnosis.

Methods: The Texome Project is studying the impact of ES in medically underserved patients who are in need of genomic testing to guide diagnosis and medical management. The hypothesis is that ES could uncover diagnoses not made by standard medical care.

Results: A 58-year-old male presented with retinitis pigmentosa, sensorineural hearing loss, and a family history of retinal diseases. A previous targeted gene panel for retinal disorders had not identified a molecular cause. ES through the Texome Project identified a novel, hemizygous variant in RPGR (NM_000328.3: c.1302dup, p.L435Sfs*18) that explained the ocular phenotype.

Conclusions: Continued genetics evaluation can help to end diagnostic odysseys of patients. Careful consideration of genes represented when utilizing gene panels is crucial to ensure an accurate diagnosis. Medically underserved populations are less likely to receive comprehensive genetic testing in their diagnostic workup. Our report is an example of the medical impact of genomic medicine implementation.

Keywords: RPGR; exome sequencing; retinal dystrophy; retinitis pigmentosa.

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Conflict of interest statement

The authors have no conflict of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Pedigree indicating a substantial family history of retinitis pigmentosa, macular degeneration, and other ocular issues in both males and females. We were only able to perform proband WES as other family members were not available for testing. Our historian for the pedigree was the proband. A&W, alive and well; d., deceased; yrs, years; blue, retinitis pigmentosum; green, hearing loss; yellow, macular degeneration.
FIGURE 2
FIGURE 2
Images taken with a Zeiss FF450plus fundus camera show classic end‐stage retinitis pigmentosa bilaterally. The camera settings were not altered between imaging of each eye. (a) Right eye, (b) left eye.
FIGURE 3
FIGURE 3
Next generation sequencing data exhibiting the single‐nucleotide duplication on all 107 reads at NM_000328.3: c.1302dup; [hg19]chrX:38156648G>GA.
See this image and copyright information in PMC

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