Reviewer ’s report  
 
Title: Novel exonic mutation inducing aberrant splicing in the IL 10RA gene and resulting in 
infantile -onset inflammatory bowel disease: a case report  
 
Version: 0 Date: 07 Dec 2015  
 
Reviewer: Holm  Uhlig  
 
Reviewer's report:  
 
This manuscript d escribes a exonic mutation in the IL10RA gene leading to infantile 
inflammatory bowel disease. This case report is - although first in Japan - largely in the line of 
several patients reported so far although some features such as thrombocytopenic purpura a nd 
transient myelomonocytic changes are interesting. The authors describe a non -synonymous 
mutation (c.537G>A, p.T179T) in IL10RA. Clinical remission was achieved after allogeneic 
hematopoietic stem cell transplantation.  
The mutation causes a splice varia nt. Splice variants have been identified using mRNA - PCR 
analysis and sequencing of PCR products. The functional consequences of the variant have been 
investigated using patient derived cells showing defective IL10 derived pSTAT3 but intact IL6 
dependent pSTAT3.  
The authors show 2 abnormal transcripts. It is important to explain/discuss in the manuscript, 
why product #2, that has expected size, and - as expected possessed a c.537G>A mutation - but 
but shows normal splicing between exon 4 and 5 cannot not rescue the IL10 signalling in 
macrophages / T cells.  
The authors may wish to comment in the manuscript that similar splice variants are described in 
the EXAC variant server so this mechanism might be an exemplar analysis.  
Are the methods appropriate and well described?  
If not, please specify what  is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not,  please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require fur ther 
assessment in your comments to the editors.  
 
Not relevant to this manuscri pt 
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competi ng interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscr ipt, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently appl ying for any patents relating to  the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have a ny other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publicat ion, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under a n Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/ 4.0/). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Novel exonic mutation inducing aberrant splicing in the IL 10RA gene and resulting in 
infantile -onset inflammatory bowel disease: a case report  
 
Version: 0 Date: 07 Dec 2015  
 
Reviewer: Holm  Uhlig  
 
Reviewer's report:  
 
This manuscript d escribes a exonic mutation in the IL10RA gene leading to infantile 
inflammatory bowel disease. This case report is - although first in Japan - largely in the line of 
several patients reported so far although some features such as thrombocytopenic purpura a nd 
transient myelomonocytic changes are interesting. The authors describe a non -synonymous 
mutation (c.537G>A, p.T179T) in IL10RA. Clinical remission was achieved after allogeneic 
hematopoietic stem cell transplantation.  
The mutation causes a splice varia nt. Splice variants have been identified using mRNA - PCR 
analysis and sequencing of PCR products. The functional consequences of the variant have been 
investigated using patient derived cells showing defective IL10 derived pSTAT3 but intact IL6 
dependent pSTAT3.  
The authors show 2 abnormal transcripts. It is important to explain/discuss in the manuscript, 
why product #2, that has expected size, and - as expected possessed a c.537G>A mutation - but 
but shows normal splicing between exon 4 and 5 cannot not rescue the IL10 signalling in 
macrophages / T cells.  
The authors may wish to comment in the manuscript that similar splice variants are described in 
the EXAC variant server so this mechanism might be an exemplar analysis.  
Are the methods appropriate and well described?  
If not, please specify what  is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not,  please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require fur ther 
assessment in your comments to the editors.  
 
Not relevant to this manuscri pt 
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competi ng interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscr ipt, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently appl ying for any patents relating to  the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have a ny other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publicat ion, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under a n Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/ 4.0/). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Novel exonic mutation inducing aberrant splicing in the IL 10RA gene and resulting in 
infantile -onset inflammatory bowel disease: a case report  
 
Version: 0 Date: 07 Dec 2015  
 
Reviewer: Holm  Uhlig  
 
Reviewer's report:  
 
This manuscript d escribes a exonic mutation in the IL10RA gene leading to infantile 
inflammatory bowel disease. This case report is - although first in Japan - largely in the line of 
several patients reported so far although some features such as thrombocytopenic purpura a nd 
transient myelomonocytic changes are interesting. The authors describe a non -synonymous 
mutation (c.537G>A, p.T179T) in IL10RA. Clinical remission was achieved after allogeneic 
hematopoietic stem cell transplantation.  
The mutation causes a splice varia nt. Splice variants have been identified using mRNA - PCR 
analysis and sequencing of PCR products. The functional consequences of the variant have been 
investigated using patient derived cells showing defective IL10 derived pSTAT3 but intact IL6 
dependent pSTAT3.  
The authors show 2 abnormal transcripts. It is important to explain/discuss in the manuscript, 
why product #2, that has expected size, and - as expected possessed a c.537G>A mutation - but 
but shows normal splicing between exon 4 and 5 cannot not rescue the IL10 signalling in 
macrophages / T cells.  
The authors may wish to comment in the manuscript that similar splice variants are described in 
the EXAC variant server so this mechanism might be an exemplar analysis.  
Are the methods appropriate and well described?  
If not, please specify what  is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not,  please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require fur ther 
assessment in your comments to the editors.  
 
Not relevant to this manuscri pt 
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competi ng interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an 
organisation that may in any way gain or lose financially from the publication of this 
manuscr ipt, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose 
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently appl ying for any patents relating to  the content of the 
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds or has applied for patents relating to the content of the manuscript?  
 
5. Do you have a ny other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below. If your reply is yes to any, please give details below.  
 
No competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included 
on my report to the authors and, if the manuscript is accepted for publicat ion, my named report 
including any attachments I upload will be posted on the website along with the authors' 
responses. I agree for my report to be made available under a n Open Access Creative Commons 
CC-BY license ( http://creativecommons.org/licenses/by/ 4.0/). I understand that any comments 
which I do not wish to be included in my named report can be included as confidential comments 
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant