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Research article
LIN LI
Capital Medical University Beijing Obstetrics and Gynecology Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3597-3350
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Purpose This study wants to know the genetic cause of preeclampsia (PE) which is a leading cause of maternal and perinatal death, but the underlying molecular mechanisms that cause PE remain poorly understood. Many single nucleotide polymorphisms have been identified by genome-wide association studies and were found to be associated with PE; however, few studies have used whole-exome sequencing (WES) to identify PE mutations.
Methods Five patients with severe early-onset preeclampsia (EOPE) were recruited, and WES was performed on each patient. Sanger sequencing was used to confirm the potential causative genetic mutation.
Results After a stringent bioinformatics analysis, a rare mutation in the GOT1 gene, c.44C>G:p.P15R, was found in one patient. Bioinformatics analysis showed that the mutation site is highly conserved across several species and was predicted to be a pathogenic mutation according to several online mutational function prediction software packages. Further structural biology homology modeling suggested that P15R would change the electric environment of enzymatic center, and might affect the binding affinity of substrate or product.
Conclusion We demonstrated for the first time that the mutation in GOT1 may be associated with EOPE, the results of this study provide researchers and clinicians with a better understanding of the molecular mechanisms that underlie maternal severe EOPE.
Keywords
preeclampsia; whole-exome sequencing; mutation; GOT1
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CURRENT STATUS: Published
View the published article at BMC Medical Genetics.
No community comments so far
Review #1 received
Received 16 Feb, 2020
Reviewer #1 agreed
On 31 Jan, 2020
Editor assigned
On 28 Jan, 2020
Reviewers invited
Invitations sent on 28 Jan, 2020
Submission checks complete
On 27 Jan, 2020
Editor invited
On 27 Jan, 2020
Version 4
Posted 23 Jan, 2020
No comments provided
Editor assigned
On 20 Jan, 2020
Editorial decision: Major revision
On 20 Jan, 2020
Submission checks complete
On 19 Jan, 2020
Editor invited
On 19 Jan, 2020
No comments provided
Editorial decision: Major revision
On 16 Jan, 2020
Review #1 received
Received 13 Jan, 2020
Reviewers invited
Invitations sent on 22 Dec, 2019
Reviewer #1 agreed
On 22 Dec, 2019
Editor assigned
On 16 Dec, 2019
Submission checks complete
On 15 Dec, 2019
Editor invited
On 15 Dec, 2019
No comments provided
Review #1 received
Received 12 Dec, 2019
Editorial decision: Major revision
On 12 Dec, 2019
Review #2 received
Received 09 Dec, 2019
Review #3 received
Received 09 Dec, 2019
Reviewer #3 agreed
On 30 Nov, 2019
Reviewer #2 agreed
On 29 Nov, 2019
Reviewer #1 agreed
On 27 Nov, 2019
Editor assigned
On 26 Nov, 2019
Reviewers invited
Invitations sent on 26 Nov, 2019
Submission checks complete
On 25 Nov, 2019
Editor invited
On 25 Nov, 2019
No comments provided
Review #2 received
Received 06 Nov, 2019
Editorial decision: Minor revision
On 06 Nov, 2019
Review #1 received
Received 26 Oct, 2019
Reviewer #2 agreed
On 23 Oct, 2019
Reviewer #1 agreed
On 13 Oct, 2019
Reviewers invited
Invitations sent on 12 Oct, 2019
Editor assigned
On 24 Sep, 2019
Submission checks complete
On 23 Sep, 2019
Editor invited
On 23 Sep, 2019
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Subject Areas
Medical Genetics
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at BMC Medical Genetics.
This is a preprint, 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
LIN LI
Capital Medical University Beijing Obstetrics and Gynecology Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3597-3350
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: Published
View the published article at BMC Medical Genetics.
No community comments so far
Review #1 received
Received 16 Feb, 2020
Reviewer #1 agreed
On 31 Jan, 2020
Editor assigned
On 28 Jan, 2020
Reviewers invited
Invitations sent on 28 Jan, 2020
Submission checks complete
On 27 Jan, 2020
Editor invited
On 27 Jan, 2020
Version 4
Posted 23 Jan, 2020
No comments provided
Editor assigned
On 20 Jan, 2020
Editorial decision: Major revision
On 20 Jan, 2020
Submission checks complete
On 19 Jan, 2020
Editor invited
On 19 Jan, 2020
No comments provided
Editorial decision: Major revision
On 16 Jan, 2020
Review #1 received
Received 13 Jan, 2020
Reviewers invited
Invitations sent on 22 Dec, 2019
Reviewer #1 agreed
On 22 Dec, 2019
Editor assigned
On 16 Dec, 2019
Submission checks complete
On 15 Dec, 2019
Editor invited
On 15 Dec, 2019
No comments provided
Review #1 received
Received 12 Dec, 2019
Editorial decision: Major revision
On 12 Dec, 2019
Review #2 received
Received 09 Dec, 2019
Review #3 received
Received 09 Dec, 2019
Reviewer #3 agreed
On 30 Nov, 2019
Reviewer #2 agreed
On 29 Nov, 2019
Reviewer #1 agreed
On 27 Nov, 2019
Editor assigned
On 26 Nov, 2019
Reviewers invited
Invitations sent on 26 Nov, 2019
Submission checks complete
On 25 Nov, 2019
Editor invited
On 25 Nov, 2019
No comments provided
Review #2 received
Received 06 Nov, 2019
Editorial decision: Minor revision
On 06 Nov, 2019
Review #1 received
Received 26 Oct, 2019
Reviewer #2 agreed
On 23 Oct, 2019
Reviewer #1 agreed
On 13 Oct, 2019
Reviewers invited
Invitations sent on 12 Oct, 2019
Editor assigned
On 24 Sep, 2019
Submission checks complete
On 23 Sep, 2019
Editor invited
On 23 Sep, 2019
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Medical Genetics
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BMC Medical Genetics.
Purpose This study wants to know the genetic cause of preeclampsia (PE) which is a leading cause of maternal and perinatal death, but the underlying molecular mechanisms that cause PE remain poorly understood. Many single nucleotide polymorphisms have been identified by genome-wide association studies and were found to be associated with PE; however, few studies have used whole-exome sequencing (WES) to identify PE mutations.
Methods Five patients with severe early-onset preeclampsia (EOPE) were recruited, and WES was performed on each patient. Sanger sequencing was used to confirm the potential causative genetic mutation.
Results After a stringent bioinformatics analysis, a rare mutation in the GOT1 gene, c.44C>G:p.P15R, was found in one patient. Bioinformatics analysis showed that the mutation site is highly conserved across several species and was predicted to be a pathogenic mutation according to several online mutational function prediction software packages. Further structural biology homology modeling suggested that P15R would change the electric environment of enzymatic center, and might affect the binding affinity of substrate or product.
Conclusion We demonstrated for the first time that the mutation in GOT1 may be associated with EOPE, the results of this study provide researchers and clinicians with a better understanding of the molecular mechanisms that underlie maternal severe EOPE.
Figure 1
Figure 2
This is a list of supplementary files associated with this preprint. Click to download.
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