Original ArticleGenomic Landscape of Sporadic Retinitis Pigmentosa: Findings from 877 Spanish Cases
Section snippets
Cohort Description
A cohort of 877 unrelated Spanish cases (475 female and 402 male participants) with no family history of retinal dystrophy was selected from the database at Fundación Jiménez Díaz University Hospital (FJD, Madrid, Spain). All patients had been referred to our unit for genetic testing because of clinical suspicion of RP. Specific exclusion criteria were as follows: (1) family pedigree compatible with AR, AD, or XL inheritance; (2) visual deficiency with onset before age 1 year and compatible
Mutation Detection Rate and Mutational Spectrum
A cohort of 877 sRP cases underwent comprehensive analysis of single nucleotide variants (SNVs) and CNVs, as detailed in the genetic algorithm in Figure 1. Likely disease-causing genotypes were identified in 330 patients, and thus the overall mutation-detection rate was 38%. A total of 304 different variants were found in 56 different genes, including 298 SNVs and 6 structural variants (SVs). Figure 2A shows the overall frequencies of disease-causing genotypes in the mutated genes. Of note, 6
Discussion
Most patients with IRD referred for routine genetic testing in Spain are sporadic cases of RP. The lack of a priori knowledge about the mode of inheritance, along with the intrinsically high clinical and genetic heterogeneity of IRD, hampers efforts to establish an accurate clinical diagnosis in these patients. In addition, doubts remain as to the likelihood that a sporadic case with an initial suspicion of IRD will have positive genetic test results. To shed light on this issue, we performed a
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2023, GeneCitation Excerpt :In the later stage, the visual field is tubular and completely blind at middle or old age. RP is inherited in a complicated mode, encompassing autosomal dominant patterns (AD, about 20 %), autosomal recessive manners (AR, about 30 %) and X-linked inheritance (XL, about 10 %), occasionally digenic modes and mitochondrial inheritance also have been reported (Kajiwara et al., 1994; Beales et al., 2003; Hartong et al., 2006; Martin-Merida et al., 2019), which further indicates the typical genetic heterogeneity of RP. Meanwhile, those without a family history were referred to as sporadic cases, and the proportion of sporadic RP is approaching 40 % (Martin-Merida et al., 2019).
Inherited retinal diseases: Linking genes, disease-causing variants, and relevant therapeutic modalities
2022, Progress in Retinal and Eye ResearchCitation Excerpt :Aiming to tabulate a list of the most common reported IRD-related disease-causing variants and genes worldwide, we performed a literature search using google scholar for relevant key words (retina, genes, cohort, mutation, disease, pathogenic, variants, identified, IRD, inherited retinal disease) and obtained a list of 748 hits. We subsequently excluded 515 irrelevant papers from the list (e.g. focused on topics other than IRDs, described IRD variants in a small cohort of patients, etc.) and the remaining 233 papers were screened for those detailing specific sequence variant information for relatively large cohorts of over 35 cases (a total of 31 papers-the “IRD cohort papers”; Table 2) (Abu-safieh et al., 2013; Birtel et al., 2018; Carss et al., 2017; Colombo et al., 2021; Ellingford et al., 2016; Ezquerra-Inchausti et al., 2018; Gao et al., 2021; Haer-Wigman et al., 2017; Holtan et al., 2020; Huang et al., 2015; Hull et al., 2020; Jespersgaard et al., 2019; Koyanagi et al., 2019; Lenassi et al., 2020; Martin-Merida et al., 2019; Nassisi et al., 2018; Perea-Romero et al., 2021; Rodríguez-muñoz et al., 2020; Sallum et al., 2020; Sharon et al., 2020; Stone et al., 2017; Wang et al., 2013, 2015, 2018, 2019; Wang et al., 2019; Weisschuh et al., 2020a; Xu et al., 2014; Zampaglione et al., 2020; Zeitz et al., 2019; Zernant et al., 2011, 2017). We then extracted genetic information from tables that were provided in the IRD cohort papers to obtain the total number of solved cases and their reported disease-causing variants.
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Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
I.M.M. and O.Z..: Sponsored by the CIBERER.
M.dP.: Supported by a PhD fellowship from the Conchita Rábago Foundation.
M.C.: Supported by the Miguel Servet Program (CPII17_00006) from ISCIII.
Supported by grants from the Instituto de Salud Carlos III (ISCIII) of the Spanish Ministry of Health, including the Center for Biomedical Research Network on Rare Diseases (CIBERER 06/07/0036), FIS (PI16/00425), and IIS-FJD Biobank PT13/0010/0012; and from Regional Government of Madrid (CAM, B2017/BMD37), all partially supported by FEDER (European Regional Development Fund). The Spanish National Organization for the Blind (ONCE), the Spanish Fighting Blindness Foundation (FUNDALUCE), University Chair UAM-IIS-FJD of Genomic Medicine, and the Ramon Areces Foundation supported our work.
HUMAN SUBJECTS: Human subjects were included in this study. The human ethics committees at the IIS-Fundacion Jimenez Diaz University Hospital approved the study. All research adhered to the tenets of the Declaration of Helsinki. All participants provided informed consent.
No animal subjects were used in this study.
Author Contributions:
Conception and design: Martin-Merida, Corton, Ayuso
Analysis and interpretation: Martin-Merida, Avila-Fernandez, del Pozo-Valero, Zurita, Perez-Carro, Aguilera-Garcia, Riveiro-Alvarez, Ana Arteche, Trujillo-Tiebas, Lorda-Sanchez, Garcia-Sandoval, Corton, Ayuso
Data collection: Martin-Merida, Avila-Fernandez, Blanco-Kelly, Zurita, Perez-Carro, Aguilera-Garcia, Riveiro-Alvarez, Ana Arteche, Trujillo-Tiebas, Tahsin-Swafiri, Rodriguez-Pinilla, Lorda-Sanchez, Garcia-Sandoval, Corton, Ayuso
Obtained funding: Ayuso
Overall responsibility: Martin-Merida, Avila-Fernandez, Del Pozo-Valero, Blanco-Kelly, Zurita, Perez-Carro, Aguilera-Garcia, Riveiro-Alvarez, Arteche, Trujillo-Tiebas, Tahsin-Swafiri, Rodriguez-Pinilla, Lorda-Sanchez, Garcia-Sandoval, Corton, Ayuso
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M.C. and C.A. have contributed equally.