The first reported case of a deletion of the entire RPGR gene in a family with X-linked retinitis pigmentosa

Mihailovic, Nataša; Schimpf-Linzenbold, Simone; Sattler, Inga; Eter, Nicole; Heiduschka, Peter

doi:10.1080/13816810.2022.2083181

Cited by 3 publications

(3 citation statements)

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“…Few patients suffered from XLRP due to a complete segmental deletion of the RPGR gene, which has not been reported in China. In a recent article, Mihailovic N et al reported for the first time a Caucasian male patient who exhibited RP due to a complete segmental deletion of the X-linked RPGR gene, accompanied by a deletion of approximately 378 kb of gene segment Xp11.4 (37814711_38192813) of the Xp11.4 chromosome (Mihailovic et al, 2022). In contrast, in the proband in this study, in addition to the complete segmental deletion of the RPGR gene, there was also a complete segmental deletion of the CYBB and XK genes in the Xp21.1 region.…”

Section: Discussionmentioning

confidence: 99%

Xp21 DNA microdeletion syndrome in a Chinese family: clinical features show retinitis pigmentosa and chronic granuloma

Li,

Hu,

et al. 2024

Front. Genet.

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Xp21 DNA microdeletion syndrome is a very rare disease characterized by retinitis pigmentosa (RP), chronic granulomatous disease (CGD), and McLeod syndrome (MLS). Due to the complex and diverse clinical manifestations, early diagnosis remains a challenge for many physicians. In this study, for the purpose of determining the pathogenic gene variants and definitive diagnosis in a patient medically backgrounded with RP and CGD from a normal Chinese family, whole-exome sequencing (WES) was performed in this proband and copy number variation (CNV) was further verified in other family members by qPCR. A genetic evaluation revealed that the short arm of the X chromosome in the proband had a deletion CNV Xp21.1p11.4 (37431123–38186681) of approximately 0.755 Mb in size, and contained three contiguous OMIM genes as X-linked Kx blood group antigen (XK), cytochrome b-245 beta chain (CYBB), and RP GTPase regulator (RPGR). The qPCR results confirmed the copy number loss in Xp21.1p11.4 present in the proband and his unaffected mother. According to the American College of Medical Genetics and Genomics (ACMG) guidelines for the CNV interpretation, the deletion of this segment was a pathogenic variant. Our results provided evidence that CNV deletion of Xp21.1p11.4 in the short arm of the X chromosome was a pathogenic variant in such Chinese RP and CGD family, and the McLeod phenotype was not yet available. This study suggests that genetic testing is essential for a definitive diagnosis, which should better assist physicians in prediction, diagnosis, genetic counseling, and guidance for Xp21 DNA microdeletion syndrome.

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Section: Discussionmentioning

confidence: 99%

Xp21 DNA microdeletion syndrome in a Chinese family: clinical features show retinitis pigmentosa and chronic granuloma

Li,

Hu,

et al. 2024

Front. Genet.

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“…Further identification of responsible underlying genes through genetic testing of diagnosed patients and their registration in worldwide databases (Leiden Open Variation Database: www. databases.lovd.nl; RetNet: www.sph.uth.edu; eyeGENE network: www.eyegene.nih.gov) could expand the ground for gene therapy of this disease [43][44][45][46].…”

Section: Genetic Pathologymentioning

confidence: 99%

X-Linked Retinitis Pigmentosa Gene Therapy: Preclinical Aspects

Mansouri

2022

Ophthalmol Ther

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The most common inherited eye disease is retinitis pigmentosa (RP). X-linked RP (XLRP) is one of the most severe types of RP, with a considerable disease burden. Patients with XLRP experience a decrease in their vision and become blind in their 4th decade of life, causing much morbidity after starting a rather normal life. Treatment of XLRP remains challenging, and current treatments are not effective enough in restoring vision. Gene therapy of XLRP, capable of restoring the functional RPGR gene, showed promising results in preclinical studies and clinical trials; however, to date, no approved product has entered the market. The development of a gene therapy product needs through preliminary assessment of the drug in animal models before administration to humans. In this article, we reviewed the genetic pathology of XLRP, along with the preclinical aspects of the XLRP gene therapy, animal models, associated assessments, and future challenges and directions.

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“…Retinitis pigmentosa GTPase regulator ( RPGR ), located on Xp11.4, is associated with a wide phenotypic spectrum of retinal disease s , including retinitis pigmentosa 3(MIM300029), X‐linked retinitis pigmentosa and sinorespiratory infections with or without deafness (MIM300455), X‐linked cone‐rod dystrophy (MIM304020), and X‐linked atrophic macular degeneration (MIM300834) (Ayyagari et al., 2002 ; Demirci et al., 2002 ; Roepman et al., 1996 ; Zito et al., 2003 ). Pathogenic variants in RPGR have been reported to cause nearly two‐thirds of all X‐linked retinitis pigmentosa (Khanna et al., 2005 ; Mihailovic et al., 2022 ; Vervoort et al., 2000 ). Individuals with RPGR ‐related X‐linked retinitis pigmentosa (XLRP) have an aggressive form of the disease, characterized by night blindness in the first or second decades of life, followed by progressive loss of visual acuity and legal blindness by the third or fourth decades of life (Di Iorio et al., 2020 ; Georgiou et al., 2021 ; Nguyen et al., 2020 ; Sandberg et al., 2007 ).…”

Section: Introductionmentioning

confidence: 99%

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

German,

Vuocolo,

Vossaert

et al. 2024

Molec Gen & Gen Med

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BackgroundThe 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.MethodsThe 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.ResultsA 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.ConclusionsContinued 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.

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The first reported case of a deletion of the entire RPGR gene in a family with X-linked retinitis pigmentosa

Cited by 3 publications

References 9 publications

Xp21 DNA microdeletion syndrome in a Chinese family: clinical features show retinitis pigmentosa and chronic granuloma

Xp21 DNA microdeletion syndrome in a Chinese family: clinical features show retinitis pigmentosa and chronic granuloma

X-Linked Retinitis Pigmentosa Gene Therapy: Preclinical Aspects

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

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