Genotype–Phenotype Analysis of RPGR Variations: Reporting of 62 Chinese Families and a Literature Review

Yang, Junfeng; Zhou, Lin; Ouyang, Jiamin; Xiao, Xueshan; Sun, Wenmin; Li, Shiqiang; Zhang, Qingjiong

doi:10.3389/fgene.2021.600210

Cited by 12 publications

(9 citation statements)

References 159 publications

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“…CDIP was negative to all 60 studied mutations, however a hemizygous missense variant, c.292C > A (p.H98N), was identi ed in RPGR exon 4. This variant was reported thus far in one case 17 . Another variant in the same nucleotide, c.292C > G (p.H98D), was reported previously to cause RP and to affect RPGR interaction with RAB28 and RPGRIP1.…”

Section: Interesting Patientsmentioning

confidence: 69%

Simultaneous Detection of Common Founder Mutations using a Cost- Effective Deep Sequencing Panel

Shalom

Hanany

Eilat

et al. 2023

Preprint

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Inherited retinal diseases (IRDs) are a clinically and genetically heterogeneous group of diseases which cause visual loss due to Mendelian mutations in over 250 genes, making genetic diagnosis challenging and time-consuming. Here we developed a new tool, CDIP (Cost-effective Deep-sequencing IRD Panel) in which a simultaneous sequencing of common mutations is performed. CDIP is based on simultaneous amplification of amplify 47 amplicons harboring common mutations followed by next generation sequencing (NGS). Following five rounds of calibration of NGS-based steps, CDIP was used in 740 IRD samples. The analysis revealed 151 mutations in 131 index cases. In 54 (7%) of these cases, CDIP identified the genetic cause of disease (the remaining were single heterozygous recessive mutations). These include a patient that was clinically diagnosed with retinoschisis and found to be homozygous for NR2E3-c.932G > A (p.R311Q) and a patient with RP who is hemizygous for an RPGR variant, c.292C > A (p.H98N), that was not included in the analysis but is located in proximity to one of these mutations. CDIP is a cost-effective deep sequencing panel for simultaneous detection of common founder mutations. This protocol can be implemented for additional populations as well as additional inherited diseases, and mainly in populations with strong founder effects.

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Section: Interesting Patientsmentioning

confidence: 69%

Simultaneous Detection of Common Founder Mutations using a Cost- Effective Deep Sequencing Panel

Shalom

Hanany

Eilat

et al. 2023

Preprint

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“…The onset of XLRP was earlier than that of autosomal RP, usually in childhood or adolescence, with a mean age of 7.2 ± 1.7 years (Hussels-Maumenee et al, 1975), and patients with XLRP usually presented with a more severe disease. Male subjects carrying the RPGR gene variant usually suffered from night blindness early in life, with rapid and severe progressive loss of peripheral vision, followed by progressive loss of central vision in the second to fourth decades life, which could progress to legal blindness (Salvetti et al, 2021;Yang et al, 2021). Clinical features were characterized by bone spicule pigmentation, attenuation of retinal vessels, waxy pallor of the optic nerve, and electroretinogram (ERG) abnormalities (Verbakel et al, 2018).…”

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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“…Our results are based on a Chinese cohort. Although Junxin Yang et al also reports a genotype–phenotype analysis of RPGR variations in a Chinese cohort ( Yang et al, 2021 ), their results mainly reveal that most of the pathogenic variants of RPGR are truncations. Our genetic analysis reveals that these variants are distributed in 10 different subregions of RPGR, and 70.59% of the variants are distributed in exon 15.…”

Section: Discussionmentioning

confidence: 99%

Mutation Analysis of the RPGR Gene in a Chinese Cohort

et al. 2022

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Purpose: The purpose of this study was to investigate the clinical and genetic characteristics of the retinitis pigmentosa GTPase regulatory factor gene (RPGR) in a Chinese cohort.Methods: A retrospective analysis was performed on 80 subjects with RPGR-retinal dystrophy (RPGR-RD) for detailed genetic and clinical characterization. The panel-based next-generation sequencing of 792 causative genes involved in common genetic eye diseases was conducted in all individuals, followed by clinical variant interpretation. Information, including age, sex, geographic distribution, family history, consanguineous marriage, age at symptom onset, disease duration, best corrected visual acuity (BCVA), and complete ophthalmologic examination results, was collected.Results: This cohort (41 men and 39 women) included 26 families (26 probands and their available family members) and 13 sporadic cases. The average age of these participants was 36.35 ± 17.68 years, and the majority of the families were from eastern China (28 families, 71.79%). The average duration of disease in the probands was 22.68 ± 15.80 years. In addition, the average BCVA values of the right and left eyes in the probands were 0.96 ± 0.77 and 1.00 ± 0.77, respectively. A total of 34 RPGR variants were identified, including 6 reported variants and 28 novel variants. Among these variants, NM_001034853.1: c.2899_2902delGAAG and c.2744_2745ins24 were considered de novo variants. The majority of the RPGR variants were classified as likely pathogenic, accounting for 70.59% of the variants (24 variants). The most common nucleotide and amino acid changes identified in this study were deletions (16 variants, 45.06%) and frameshifts (17 variants, 50.00%), respectively. Genetic analysis revealed that these RPGR variants were distributed in 10 different subregions of RPGR, and 70.59% of the RPGR variants (24 variants) were located in exon 15. Four RPGR variants, NM_001034853.1: c.2405_2406delAG, c.1345C > T, c.2218G > T and c.2236_2237delGA, occurred at a very high frequency of 28.21% (11 families) among 39 unrelated families.Conclusion: This study expands the known mutational spectrum of RPGR, and we provide a new reference for the genetic diagnosis of RPGR variants.

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Genotype–Phenotype Analysis of RPGR Variations: Reporting of 62 Chinese Families and a Literature Review

Cited by 12 publications

References 159 publications

Simultaneous Detection of Common Founder Mutations using a Cost- Effective Deep Sequencing Panel

Simultaneous Detection of Common Founder Mutations using a Cost- Effective Deep Sequencing Panel

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

Mutation Analysis of the RPGR Gene in a Chinese Cohort

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