Elsevier

Ophthalmology

Volume 126, Issue 11, November 2019, Pages 1549-1556
Ophthalmology

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

https://doi.org/10.1016/j.ophtha.2019.04.038Get rights and content

Purpose

To characterize the genetic landscape of patients with suspected retinitis pigmentosa (RP) in the Chinese population.

Participants

A total of 1243 patients of Chinese origin with clinically suspected RP and their available family members (n = 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 (6–16 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 China.

Section snippets

Study Subjects and Ethics Statement

The current study was approved by the Ethics Committee of the Eye and ENT Hospital of Fudan University and conformed to the tenets of the Declaration of Helsinki. Written informed consent was obtained from all participants or their guardians. A total of 1243 patients and their available family members (total participants: 2701) who visited the Department of Ophthalmology and Visual Sciences at the Eye and ENT Hospital of Fudan University, China, between January 2016 and August 2018, and who

Cohort Characteristics

A total of 1243 patients (611 female, 632 male) with clinically suspected IRD were recruited, of whom most are unrelated probands (869/1243). The mean patient age was 39.8±17.8 years (range, 0.83–87; median, 40), and participants came from all over China. The age of onset was known in 968 patients, and they were divided into 3 subgroups (Table 1); patients with positive variants in more than 1 gene were not included in the 3 groups.

Diagnostic Yield and Genetic Findings

Overall, 72.08% (896/1243) of patients received a confirmed

Discussion

Since the launch of the Precision Medicine (PM) Initiative in early 2015, PM has already made important strides in patient care, including the prevention, diagnosis, and treatment of diseases.18, 19 Genetic analysis plays a vital role in facilitating this, although it is not the only path to PM.20 In this study, we performed genetic analysis in 2701 subjects, making it the largest Asian RP cohort to our knowledge.21, 22, 23, 24, 25 Moreover, the patients came from all over China and have a

Acknowledgments

The authors thank all of the participants in this study for their collaboration, the technical staff at Eye and ENT Hospital of Fudan University for assistance, and Beijing Genomics Institute Shenzhen for technical support. The data that support the findings of this study have been deposited in the CNSA (https://db.cngb.org/cnsa/) of CNGBdb with accession number CNP0000453.

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  • Cited by (78)

    • Genetic characteristics of suspected retinitis pigmentosa in a cohort of Chinese patients

      2023, Gene
      Citation Excerpt :

      About half of the genetically solved cases were attributed to variants in 3 genes: USH2A, CYP4V2 and RPGR. And the most common of the known pathogenic genes of RP detected in this present work was USH2A, which was consistent with previous reports in Chinese (Huang et al., 2017; Gao et al., 2019; Dan et al., 2020). However, EYS was the most frequently detected gene in Japanese RP patients (Oishi et al., 2014) and FAM161A had the highest mutation frequency in the Israeli-Jewish population (Beryozkin et al., 2020).

    View all citing articles on Scopus

    Supplemental material available at www.aaojournal.org.

    Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

    Supported by the National Natural Science Foundation of China (Grants NSFC81770944, 81770925, 81790641, the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences 2018PT32019). Natural Science Foundation of Guangdong Province (NO.2015A030313472), Shenzhen Engineering Laboratory for Birth Defects Screening, DRC-SZ [2016]750, Shenzhen Municipal Government of China JCYJ20180703093402288, a GRF grant from Hong Kong government Project No. [CityU 11256116] and a SRG grant from City University of Hong Kong Project No.[7005058].

    HUMAN SUBJECTS: Human subjects were included in this study. The human ethics committees at the Eye and ENT Hospital of Fudan University 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: Wu, Xu

    Data collection: Gao, Li, Chen, Hu, Zhang, Qi, Xu, Wang, Chang, Zhang, Liu, Wang, Xu, Wu

    Analysis and interpretation: Gao, Li, Chen, Hu, Zhang, Qi, Xu, Wang, Li, Chen, Wu

    Obtained funding: Wu, Xu, Chen

    Overall responsibility: Gao, Chen

    F.-.J.G., J.-K.L., H.C., and J-H.W. contributed equally to this work.

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