Review for 10.1186/s12876-016-0424-5 (2016)

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  
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