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Research article
zhenghui wang
Xi'an Jiaotong University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5630-7277
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKⅡ proteins in the skin lesions of HHD patients.
Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined.
Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKⅡ levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKⅡ levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.
Keywords
Familial benign chronic pemphigus, ATP2C1, gene mutation, p63
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View the published article at BMC Medical Genetics.
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On 18 May, 2020
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On 13 May, 2020
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Editorial decision: Minor revision
On 12 May, 2020
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Editorial decision: Minor revision
On 05 May, 2020
Review #1 received
Received 30 Apr, 2020
Reviewer #1 agreed
On 29 Apr, 2020
Editor assigned
On 28 Apr, 2020
Reviewers invited
Invitations sent on 28 Apr, 2020
Editor invited
On 27 Apr, 2020
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On 28 Feb, 2020
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Editorial decision: Major revision
On 03 Apr, 2020
Review #2 received
Received 02 Apr, 2020
Review #1 received
Received 01 Apr, 2020
Reviewer #2 agreed
On 26 Mar, 2020
Reviewer #1 agreed
On 15 Mar, 2020
Reviewers invited
Invitations sent on 14 Mar, 2020
First submitted
On 25 Feb, 2020
Editor assigned
On 25 Feb, 2020
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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
zhenghui wang
Xi'an Jiaotong University
Corresponding Author
ORCiD: https://orcid.org/0000-0002-5630-7277
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.
Version 6
Posted 21 May, 2020
No community comments so far
Editorial decision: Accept
On 20 May, 2020
No comments provided
Editorial decision: Minor revision
On 18 May, 2020
No comments provided
Editorial decision: Minor revision
On 13 May, 2020
No comments provided
Editorial decision: Minor revision
On 12 May, 2020
No comments provided
Editorial decision: Minor revision
On 05 May, 2020
Review #1 received
Received 30 Apr, 2020
Reviewer #1 agreed
On 29 Apr, 2020
Editor assigned
On 28 Apr, 2020
Reviewers invited
Invitations sent on 28 Apr, 2020
Editor invited
On 27 Apr, 2020
Submission checks complete
On 28 Feb, 2020
No comments provided
Editorial decision: Major revision
On 03 Apr, 2020
Review #2 received
Received 02 Apr, 2020
Review #1 received
Received 01 Apr, 2020
Reviewer #2 agreed
On 26 Mar, 2020
Reviewer #1 agreed
On 15 Mar, 2020
Reviewers invited
Invitations sent on 14 Mar, 2020
First submitted
On 25 Feb, 2020
Editor assigned
On 25 Feb, 2020
Submission checks complete
On 24 Feb, 2020
Editor invited
On 24 Feb, 2020
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.
Background: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKⅡ proteins in the skin lesions of HHD patients.
Methods: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined.
Results: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKⅡ levels. Conclusion: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKⅡ levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
This is a list of supplementary files associated with this preprint. Click to download.
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