Identification of novel X-linked gain-of-function RPGR-ORF15 mutation in Italian family with retinitis pigmentosa and pathologic myopia

Parmeggiani, Francesco; Barbaro, V.; Nadai, Katia De; Lavezzo, Enrico; Toppo, Stefano; Chizzolini, Marzio; Palù, Giorgio; Parolin, Cristina; Iorio, Enzo Di

doi:10.1038/srep39179

Cited by 22 publications

(13 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Multiple studies have shown that female heterozygous RPGR mutation carriers had early-onset high myopia in one of two eyes, especially those with protein truncating variants (Jin et al 2006;Yokoyama et al 2001). Some families showed even full penetrance of high myopia in heterozygous carriers (Parmeggiani et al 2016). Both patients with a RPGR mutation are female carriers in our study.…”

Section: Discussionsupporting

confidence: 59%

Peer Review #3 of "Exome sequencing study of 20 patients with high myopia (v0.2)"

2018

View full text Add to dashboard Cite

Background. High myopia is a common ocular disease worldwide. To expand our current understanding of the genetic basis of high myopia, we carried out a whole exome sequencing study to identify potential causal gene mutations. Methods. A total of 20 individuals with high myopia were exome sequenced. A novel filtering strategy combining phenotypes and functional impact of variants was applied to identify candidate genes by multi-step bioinformatics analyses. Network and enrichment analysis were employed to examine the biological pathways involved in the candidate genes. Results. In 16 out of 20 patients, we identified 20 potential pathogenic gene variants for high myopia. 18 variants were located in myopia-associated chromosomal regions. In addition to the novel mutations found in 5 known myopia genes (ADAMTS18, CSMD1, P3H2, RPGR, and SLC39A5), we also identified pathogenic variants in 7 ocular disease genes (ABCA4, CEP290, HSPG2, PCDH15, SAG, SEMA4A, and USH2A) as novel candidate genes. The biological processes associated with vision were significantly enriched in our candidate genes, including visual perception, photoreceptor cell maintenance, retinoid metabolic process, and cellular response to zinc ion starvation. Discussion. Systematic mutation analysis of candidate genes was performed using whole exome sequencing (WES) data, functional interaction (FI) network, GO and pathway enrichment. FI network analysis revealed important network modules and regulator linker genes (EP300, CTNNB1) potentially related to high myopia development. Our study expanded the list of candidate genes associated with high myopia, which increased the genetic screening performance and provided implications for future studies on the molecular genetics of myopia.

show abstract

Section: Discussionsupporting

confidence: 59%

Peer Review #3 of "Exome sequencing study of 20 patients with high myopia (v0.2)"

2018

View full text Add to dashboard Cite

show abstract

“…Multiple studies have shown that female heterozygous RPGR mutation carriers had early-onset high myopia in one of two eyes, especially those with protein truncating variants ( Jin et al, 2006 ; Yokoyama et al, 2001 ). Some families showed even full penetrance of high myopia in heterozygous carriers ( Parmeggiani et al, 2016 ). Both patients with a RPGR mutation are female carriers in our study.…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing study of 20 patients with high myopia

Wan

Deng

et al. 2018

PeerJ

View full text Add to dashboard Cite

BackgroundHigh myopia is a common ocular disease worldwide. To expand our current understanding of the genetic basis of high myopia, we carried out a whole exome sequencing (WES) study to identify potential causal gene mutations.MethodsA total of 20 individuals with high myopia were exome sequenced. A novel filtering strategy combining phenotypes and functional impact of variants was applied to identify candidate genes by multi-step bioinformatics analyses. Network and enrichment analysis were employed to examine the biological pathways involved in the candidate genes.ResultsIn 16 out of 20 patients, we identified 20 potential pathogenic gene variants for high myopia. A total of 18 variants were located in myopia-associated chromosomal regions. In addition to the novel mutations found in five known myopia genes (ADAMTS18, CSMD1, P3H2, RPGR, and SLC39A5), we also identified pathogenic variants in seven ocular disease genes (ABCA4, CEP290, HSPG2, PCDH15, SAG, SEMA4A, and USH2A) as novel candidate genes. The biological processes associated with vision were significantly enriched in our candidate genes, including visual perception, photoreceptor cell maintenance, retinoid metabolic process, and cellular response to zinc ion starvation.DiscussionSystematic mutation analysis of candidate genes was performed using WES data, functional interaction (FI) network, Gene Ontology and pathway enrichment. FI network analysis revealed important network modules and regulator linker genes (EP300, CTNNB1) potentially related to high myopia development. Our study expanded the list of candidate genes associated with high myopia, which increased the genetic screening performance and provided implications for future studies on the molecular genetics of myopia.

show abstract

“…More specifically, the eyes with the RPGR gene had the steepest curvature compared to the other ciliopathy-related Downloaded from iovs.arvojournals.org on 11/03/2020 genes. Earlier studies have reported the findings in RPGR eyes complicated by high myopia [28][29][30][31] and on the relationship between RPGR-related RP and pathologic myopia. 31,32 However, the macular curvature in these eyes was not mentioned.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Macular Curvature and Common Causative Genes of Retinitis Pigmentosa in Japanese Patients

Koyanagi

Ueno

Ito

et al. 2020

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

PURPOSE. To determine the relationship between the macular curvature and the causative genes of retinitis pigmentosa (RP). METHODS. We examined the medical records of the right eyes of 65 cases with RP (31 men and 34 women; average age, 47.6 years). There were 31 cases with the EYS variants, 11 cases with the USH2A variants, six cases with the RPGR variants, 13 cases with the RP1 variants, and four cases with the RP1L1 variants. The mean curvature of Bruch's membrane was calculated within 6 mm of the fovea as the mean macular curvature index (MMCI, 1/μm). We used multiple linear regression analysis to determine the independence of the causative genes contributing to the MMCIs after adjustments for age, sex, axial length, and width of the ellipsoid zone. RESULTS. The median MMCI was −31.2 × 10 −5 /μm for the RPGR eyes, −16.5 × 10 −5 /μm for the RP1L1 eyes, −13.0 × 10 −5 /μm for the RP1 eyes, −9.8 × 10 −5 /μm for the EYS eyes, and −9.0 × 10 −5 /μm for the USH2A eyes. Compared with the EYS gene as the reference gene, the RPGR gene was significantly related to the MMCI values after adjusting for the other parameters (P = 5.30 × 10 −6). In contrast, the effects of the other genes, USH2A, RP1, and RP1L1, were not significantly different from that of the EYS gene (P = 0.26, P = 0.49, and P = 0.92, respectively). CONCLUSIONS. The RPGR gene had a stronger effect on the steep macular curvature than the other ciliopathy-related genes.

show abstract

Identification of novel X-linked gain-of-function RPGR-ORF15 mutation in Italian family with retinitis pigmentosa and pathologic myopia

Cited by 22 publications

References 43 publications

Peer Review #3 of "Exome sequencing study of 20 patients with high myopia (v0.2)"

Peer Review #3 of "Exome sequencing study of 20 patients with high myopia (v0.2)"

Exome sequencing study of 20 patients with high myopia

Relationship Between Macular Curvature and Common Causative Genes of Retinitis Pigmentosa in Japanese Patients

Contact Info

Product

Resources

About