Review for 10.1186/s12876-020-01237-8 (2020)

Reviewer ’s report  
 
Title: NEW MUTATION OF THE CERU LOPLASMIN GENE IN THE CASE OF A 
NEUROLOGICALLY ASYMPTOMATIC PATIENT W ITH MICROCYTIC ANAEMIA, 
OBESITY AND SUPPOSED WILSON ’S DISEASE  
 
Version: 0 Date: 04 Jan 2020  
 
Reviewer: Ludmila Puchkova  
 
Reviewer's report:  
 
The article "New mutation of the ceruloplas min gene in case of a neurologically asymptomatic 
patient with microcytic anaemia and steatosis of liver" by M. Ondrejkovičová et al. describes the 
homozygous substitution c.1664G &gt; A in the CP gene associated with a non -synonymous 
substitution in the CP  protein Gly555Glu in a patient with microcytic hypochromic anemia 
without clinical symptoms of a neurodegeneration. In the patient, biochemical hallmarks of iron 
dyshomeostasis were revealed (an increase in ferritin in the blood, an increase in the 
concen tration of iron in the liver as well as the deposition of iron in the brain). Iron 
dyshomeostasis developed against a background of low CP levels in the serum blood. The 
authors determined the primary structure of the ATP7B gene, whose mutations are respon sible 
for the development of Wilson's disease, characterized by a low level of CP. They also tested 
most frequent mutations in HFE TRF2 and FPN1 genes, responsible for the development of 
hereditary hemochromatosis (iron overload). These checks gave a negat ive result.  
 
Full sequencing of the CP gene revealed a new mutation. The authors attribute this mutation with 
the development of symptoms in the patient. Iron chelation therapy partially normalized the shift 
iron metabolism in the blood serum.  
 
An algorithm  for finding the genetic cause of a shift in iron metabolism based on biochemical 
parameters does not cause any comments. The description of new mutations in the CP gene 
associated with pathological phenotypes contributes to a better understanding of the n ature of 
diseases associated with impaired copper homeostasis and the biological role of ceruloplasmin, a 
moonlighting protein.  
 
 
Major notes  
 
The authors should clarify whether CP is reduced due to the decrease of serum oxidase activity 
or the immunoreactive CP concentration. A method for determining the CP level needs to be 
added.  
 
The authors do not analyze the consequences of substitution Gly5 55Glu for folding CP and its 
enzymatic and other biological properties. In silico CP(Gly555Glu) analysis would be 
appropriate.  
 
Minor points:  
 
Line 69: after words: "serum ceruloplasmin", the patient value of CP concentration must be 
added.  
 
Line 75 - specify  whether the ATP7B cDNA or ATP7B chromosomal gene was sequenced.  
 
Line 76 - add standard copper concentration (ug copper/gram of dry liver tissue ± SD)  
 
A more thorough grammar and style check is necessary (e.g. Line 34 -., Line 111 - tranferrin; 
Line 212 - mappiong, Line 40 - "with very little low values" - tautology, etc.).  
 
A formal review of the correspondence of the manuscript to the "CARE Checklist" showed that  
 
1. The words: "case report" must be added in the title;  
 
2. Words: "case report" must be added  to "Key words";  
 
3. The topic "Introduction" is absent. There is a topic "Background", the references are absent.  
 
4. The topic "Case presentation" must be renamed to "Patient presentation"  
 
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 stat istics in the manus cript or would you recommend an 
additional statistical review?  
If an additional statistical review is recommended, please speci fy what aspects require further 
assessment in your comments to the editors.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
Needs some language corrections before being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1.  Have you in the past five years received reimbursements, f ees, funding, or salary 
from an organisation that may in any way gain or lose financially from the 
publi cation of this manuscript, either now or in the future?  
 
2.  Do you hold any stocks or shares in an organisation t hat 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 curr ently applying 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 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 interests  
 
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