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

Feng-Juan Gao; Jian-Kang Li; Han Chen; Fang-Yuan Hu; Sheng-Hai Zhang; Yu-He Qi; Ping Xu; Dan-Dan Wang; Lu-Sheng Wang; Qing Chang; Yong-Jin Zhang; Wei Liu; Wei Li; Min Wang; Fang Chen; Ge-Zhi Xu; Ji-Hong Wu

doi:10.1016/j.ophtha.2019.04.038

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

Feng-Juan Gao, Jian-Kang Li, Han Chen, Fang-Yuan Hu, Sheng-Hai Zhang, Yu-He Qi, Ping Xu, Dan-Dan Wang, Lu-Sheng Wang, Qing Chang, Yong-Jin Zhang, Wei Liu, Wei Li, Min Wang, Fang Chen, Ge-Zhi Xu, Ji-Hong Wu^*

^*Corresponding author for this work

Genome Research and Molecular Bio Medicine

20 Citations (Scopus)

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 = 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.

Original language	English
Journal	Ophthalmology
Volume	126
Issue number	11
Pages (from-to)	1549-1556
Number of pages	8
ISSN	0161-6420
DOIs	https://doi.org/10.1016/j.ophtha.2019.04.038
Publication status	Published - Nov 2019

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Gao, F.-J., Li, J.-K., Chen, H., Hu, F.-Y., Zhang, S.-H., Qi, Y.-H., Xu, P., Wang, D.-D., Wang, L.-S., Chang, Q., Zhang, Y.-J., Liu, W., Li, W., Wang, M., Chen, F., Xu, G.-Z., & Wu, J.-H. (2019). Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa. Ophthalmology, 126(11), 1549-1556. https://doi.org/10.1016/j.ophtha.2019.04.038

@article{4d3efb12ea0d496ea4c1291847351670,

title = "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 = 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.",

author = "Feng-Juan Gao and Jian-Kang Li and Han Chen and Fang-Yuan Hu and Sheng-Hai Zhang and Yu-He Qi and Ping Xu and Dan-Dan Wang and Lu-Sheng Wang and Qing Chang and Yong-Jin Zhang and Wei Liu and Wei Li and Min Wang and Fang Chen and Ge-Zhi Xu and Ji-Hong Wu",

year = "2019",

month = nov,

doi = "10.1016/j.ophtha.2019.04.038",

language = "English",

volume = "126",

pages = "1549--1556",

journal = "Ophthalmology",

issn = "0161-6420",

publisher = "Elsevier",

number = "11",

}

TY - JOUR

T1 - Genetic and Clinical Findings in a Large Cohort of Chinese Patients with Suspected Retinitis Pigmentosa

AU - Gao, Feng-Juan

AU - Li, Jian-Kang

AU - Chen, Han

AU - Hu, Fang-Yuan

AU - Zhang, Sheng-Hai

AU - Qi, Yu-He

AU - Xu, Ping

AU - Wang, Dan-Dan

AU - Wang, Lu-Sheng

AU - Chang, Qing

AU - Zhang, Yong-Jin

AU - Liu, Wei

AU - Li, Wei

AU - Wang, Min

AU - Chen, Fang

AU - Xu, Ge-Zhi

AU - Wu, Ji-Hong

PY - 2019/11

Y1 - 2019/11

N2 - 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 = 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.

AB - 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 = 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.

U2 - 10.1016/j.ophtha.2019.04.038

DO - 10.1016/j.ophtha.2019.04.038

M3 - Journal article

C2 - 31054281

AN - SCOPUS:85066490344

SN - 0161-6420

VL - 126

SP - 1549

EP - 1556

JO - Ophthalmology

JF - Ophthalmology

IS - 11

ER -

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

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