Reviewer ’s report  
 
Title: A de novo Whole Gene Deletion of XIAP Detected by Exome Sequencing Analysis in 
Very  Early Onset Inflammatory Bowel Disease: A Cas e Report  
 
Version: 0 Date: 27 Aug 2015  
 
Reviewer: Murugu  Manickam  
 
Reviewer ’s report:  
 
Interesting single case of XIAP induced inflammatory bowel disease. The mechanism is not 
previously reported though mutations in XIAP are known to be assoc iated with early -onset 
disease.  
 
It might be overstated to say that exome testing is the most effici ent method though for genetic 
diagnosis. If there is a finite number of genes associated (20 -30 even) there are customizable 
panels available to cover the genes of interest. This would allow deeper coverage of genes of 
interest (versus whole exome) and cou ld potentially include immediate CNV coverage. Results 
would also be quicker if there are fewer va riants of unknown significance.  
 
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 co ntrols?  
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 statisti cs in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questi ons: 
 
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  
manuscript, 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 applying for any patents relating to the content o f 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 any 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.  
 
I declare that I have no competing i nterests.  
 
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 publication, 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 an 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: A de novo Whole Gene Deletion of XIAP Detected by Exome Sequencing Analysis in 
Very  Early Onset Inflammatory Bowel Disease: A Cas e Report  
 
Version: 0 Date: 27 Aug 2015  
 
Reviewer: Murugu  Manickam  
 
Reviewer ’s report:  
 
Interesting single case of XIAP induced inflammatory bowel disease. The mechanism is not 
previously reported though mutations in XIAP are known to be assoc iated with early -onset 
disease.  
 
It might be overstated to say that exome testing is the most effici ent method though for genetic 
diagnosis. If there is a finite number of genes associated (20 -30 even) there are customizable 
panels available to cover the genes of interest. This would allow deeper coverage of genes of 
interest (versus whole exome) and cou ld potentially include immediate CNV coverage. Results 
would also be quicker if there are fewer va riants of unknown significance.  
 
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 co ntrols?  
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 statisti cs in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questi ons: 
 
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  
manuscript, 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 applying for any patents relating to the content o f 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 any 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.  
 
I declare that I have no competing i nterests.  
 
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 publication, 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 an 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: A de novo Whole Gene Deletion of XIAP Detected by Exome Sequencing Analysis in 
Very  Early Onset Inflammatory Bowel Disease: A Cas e Report  
 
Version: 0 Date: 27 Aug 2015  
 
Reviewer: Murugu  Manickam  
 
Reviewer ’s report:  
 
Interesting single case of XIAP induced inflammatory bowel disease. The mechanism is not 
previously reported though mutations in XIAP are known to be assoc iated with early -onset 
disease.  
 
It might be overstated to say that exome testing is the most effici ent method though for genetic 
diagnosis. If there is a finite number of genes associated (20 -30 even) there are customizable 
panels available to cover the genes of interest. This would allow deeper coverage of genes of 
interest (versus whole exome) and cou ld potentially include immediate CNV coverage. Results 
would also be quicker if there are fewer va riants of unknown significance.  
 
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 co ntrols?  
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 statisti cs in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Qualit y of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questi ons: 
 
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  
manuscript, 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 applying for any patents relating to the content o f 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 any 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.  
 
I declare that I have no competing i nterests.  
 
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 publication, 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 an 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