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Research article
Genetic investigation of 211 Chinese families expands the mutational and phenotypical spectrum in hereditary retinopathy genes through targeted sequencing technology
Xiangdong Kong
The First Affiliated Hospital of Zhengzhou University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0030-7638
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Hereditary retinopathy is a significant cause of blindness worldwide. Despite the discovery of many mutations in various retinopathies, a large part of patients remain undiagnosed genetically. Targeted next generation sequencing of the human genome is a suitable approach for retinopathy molecular diagnosis.
Methods: We described a cohort of 211 families from central China with various forms of retinopathy, 95 families of which were investigated using NGS multi-gene panel sequencing as well as the other 116 patients were LHON suspected tested by Sanger sequencing. We validated the candidate variants by PCR-based Sanger sequencing. We have made comprehensive analysis of the cases through sequencing data and ophthalmologic examination information.
Results: The potentially causal mutation was identified in majority of the families with retinopathy (57.9% of 95 families) and Leber hereditary optic neuropathy (LHON) (21.6% of 116 families). The identified mutations (68mutations, 37 of which are novel) of the 95 families spanned 31 known disease genes, about half have not been reported relation to hereditary retinopathy. The NGS panel solution provides 45.3% potential diagnostic rate of the retinopathy families and another 12.6% families detect candidate gene mutations with undefined pathogenicity in this study.
Conclusion: Our study showed novel mutations and phenotypic aspects of retinopathy, and demonstrated genetic and clinical heterogeneity of the conditions. Our results illustrated the significance of molecular genetic testing for patients with hereditary retinopathy.
Keywords
hereditary retinopathy, novel mutations, targeted sequencing, genetic testing
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CURRENT STATUS: Under Revision
Version 3
Posted 07 Jan, 2021
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Editorial decision: Major revision
On 04 Jan, 2021
Editor assigned
On 15 Dec, 2020
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On 15 Dec, 2020
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Editorial decision: Revise before sending to peer reviewers
On 07 Dec, 2020
Editor assigned
On 21 Nov, 2020
Submission checks complete
On 21 Nov, 2020
Editor invited
On 21 Nov, 2020
No comments provided
Editorial decision: Major revision
On 30 Oct, 2020
Review #2 received
Received 21 Oct, 2020
Reviewer #3 agreed
On 20 Jul, 2020
Reviewer #2 agreed
On 26 May, 2020
Review #1 received
Received 11 May, 2020
Reviewers invited
Invitations sent on 22 Apr, 2020
Reviewer #1 agreed
On 22 Apr, 2020
First submitted
On 03 Apr, 2020
Editor assigned
On 03 Apr, 2020
Submission checks complete
On 02 Apr, 2020
Editor invited
On 02 Apr, 2020
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Subject Areas
Epigenetics & Genomics
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This preprint is under consideration at BMC Medical Genomics. A preprint is a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research article
Genetic investigation of 211 Chinese families expands the mutational and phenotypical spectrum in hereditary retinopathy genes through targeted sequencing technology
Xiangdong Kong
The First Affiliated Hospital of Zhengzhou University
Corresponding Author
ORCiD: https://orcid.org/0000-0003-0030-7638
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Under Revision
Version 3
Posted 07 Jan, 2021
No community comments so far
Editorial decision: Major revision
On 04 Jan, 2021
Editor assigned
On 15 Dec, 2020
Submission checks complete
On 15 Dec, 2020
Editor invited
On 15 Dec, 2020
No comments provided
Editorial decision: Revise before sending to peer reviewers
On 07 Dec, 2020
Editor assigned
On 21 Nov, 2020
Submission checks complete
On 21 Nov, 2020
Editor invited
On 21 Nov, 2020
No comments provided
Editorial decision: Major revision
On 30 Oct, 2020
Review #2 received
Received 21 Oct, 2020
Reviewer #3 agreed
On 20 Jul, 2020
Reviewer #2 agreed
On 26 May, 2020
Review #1 received
Received 11 May, 2020
Reviewers invited
Invitations sent on 22 Apr, 2020
Reviewer #1 agreed
On 22 Apr, 2020
First submitted
On 03 Apr, 2020
Editor assigned
On 03 Apr, 2020
Submission checks complete
On 02 Apr, 2020
Editor invited
On 02 Apr, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Epigenetics & Genomics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Hereditary retinopathy is a significant cause of blindness worldwide. Despite the discovery of many mutations in various retinopathies, a large part of patients remain undiagnosed genetically. Targeted next generation sequencing of the human genome is a suitable approach for retinopathy molecular diagnosis.
Methods: We described a cohort of 211 families from central China with various forms of retinopathy, 95 families of which were investigated using NGS multi-gene panel sequencing as well as the other 116 patients were LHON suspected tested by Sanger sequencing. We validated the candidate variants by PCR-based Sanger sequencing. We have made comprehensive analysis of the cases through sequencing data and ophthalmologic examination information.
Results: The potentially causal mutation was identified in majority of the families with retinopathy (57.9% of 95 families) and Leber hereditary optic neuropathy (LHON) (21.6% of 116 families). The identified mutations (68mutations, 37 of which are novel) of the 95 families spanned 31 known disease genes, about half have not been reported relation to hereditary retinopathy. The NGS panel solution provides 45.3% potential diagnostic rate of the retinopathy families and another 12.6% families detect candidate gene mutations with undefined pathogenicity in this study.
Conclusion: Our study showed novel mutations and phenotypic aspects of retinopathy, and demonstrated genetic and clinical heterogeneity of the conditions. Our results illustrated the significance of molecular genetic testing for patients with hereditary retinopathy.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5