Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa

Abstract

Purpose: To characterize the genetic landscape of patients with suspected retinitis pigmentosa (RP) in the Chinese population.Design: Cohort study.Participants: A total of 1243 patients of Chinese origin with clinically suspected RP and their available family members (n ¼ 2701) were recruited.Methods: All patients and available family members were screened using multigene panel testing (including 586 eye disease-associated genes), followed by clinical variant interpretation.Main Outcome Measures: Diagnostic yield, the 17 most commonly implicated genes, age at onset, de novo mutations, and clinical usefulness of genetic testing.Results: Overall, 72.08% of patients received a molecular diagnosis, and the 17 top genes covered 75.63% of diagnostic cases. Diagnostic yield was higher among patients in the early-onset subgroup ( 5 years old, 79.58%) than in the childhood or adolescence-onset subgroup (6e16 years old, 73.74%) and late-onset subgroup (!17 years old, 65.99%). Moreover, different genes associated with different onset ages and subgroups with different onset ages showed a diverse mutation spectrum. Only 11 de novo mutations (3.18%) were identified. Furthermore, 16.84% of the patients who received a molecular diagnosis had refinement of the initial clinical diagnoses, and the remaining 83.16% received definite genetic subtypes of RP.Conclusions: This large cohort study provides population-based data of the genome landscape of patients with suspected RP in China. The diagnostic yield was significantly higher than that in previous studies, and the mutation spectrum is completely different with other populations. Genetic testing improves the chance to establish a precise diagnosis, identifies features not previously determined, and allows a more accurate refinement of risk to family members. Our results not only expand the existing genotypic spectrum but also serve as an efficient reference for the design of panel-based genetic diagnostic testing and genetic counseling for patients with suspected RP in

Clinical utility of genetic testing in 201 preschool children with inherited eye disorders

“…7 Also, a recent study reporting findings from 1243 IRD patients of Chinese origin reported a diagnostic yield of 72% (n = 1243). 35 Overall, these comparisons suggest that the likelihood of a genetic test identifying a molecular diagnosis are linked to (1) the current state of knowledge of the genetic architecture of the patient's condition (e.g., higher for albinism and IRD than for cataract and ASD); (2) the pretest probability of the patient having a penetrant monogenic disorder (typically higher for bilateral disease, when there is relevant family history, for specific wellrecognized clinical presentations and/or for early childhood onset conditions). 35,36 Like any other medical interventions, diagnostic genetic tests should be thoroughly evaluated before their introduction into routine practice.…”

Genetic architecture of inherited retinal degeneration in Germany: A large cohort study from a single diagnostic center over a 9‐year period

“…In the Spanish, Chinese, and German cohorts, which only comprised RP cases, an X-linked pattern of inheritance among the solved cases was observed in 7.9%, 11%, and 12.1%, respectively (Birtel et al, 2018;Gao et al, 2019;Martin-Merida et al, 2019). In contrast, X-linked cases constitute 19.2% of solved patients with RP in our cohort.…”

“…Diagnostic rates varied according to the disease type ( (Carss et al, 2017;Dockery et al, 2017;Jespersgaard et al, 2019;Sharon et al, 2020;Stone et al, 2017). In addition, for comparison purposes, we focused on two studies that investigated large cohorts of patients with RP in the Spanish and Chinese populations (Gao et al, 2019;Martin-Merida et al, 2019), respectively, and a small RP cohort study performed in the German population (Birtel et al, 2018). (2018) have analyzed 116 patients with RP.…”

“…shows an extreme level of genetic heterogeneity (Gao et al, 2019;Martin-Merida et al, 2019), with more than 90 "disease genes" reported to date (sourced from RetNet, https://sph.uth.edu/retnet, as of January 2020).…”

Design, Development and Deployment of a Web-Based Interoperable Registry for Inherited Retinal Dystrophies in Portugal -The Ird-Pt

“…Inherited retinal dystrophies (IRDs) are a clinically and genetically heterogenous group of diseases with an estimated prevalence of 1 in 3,000 individuals. [8] Despite some common ground, genetic pro les vary considerably among regions and ethnic groups, [9][10][11][12][13][14][15][16] thus highlighting the importance of obtaining reference population-based data. The presence of founder mutations may greatly contribute for these differences, as observed in a large Israeli population.…”