Genotype–Phenotype Correlation in a Couple in Which the Wife Is a Carrier of the Beta-Thalassemia Trait and the Husband Is a Carrier of a Mutation in the ALAS2 Gene: Both Gene Defects Are Associated with Non-Iron-Deficiency Microcytic Anemia
, Carmela Centoducati, Arianna Allegretti, Francesco La Rocca and Brunilde PersiaRound 1
Reviewer 1 Report
Comments and Suggestions for AuthorsComment 1: The title does not sufficiently reflect the objective or content of the report.
Comment 2: The objective needs to be improved.
Comment 3: The objective and design of the study should be presented at the end of the introduction section.
Comment 4: The source of the data used to produce the different figures and tables should be mentioned below the corresponding illustration.
Comment 5: The division of the content into sections should be reviewed and organized, so that the main sections and subsections are clear and distinct and do not interfere.
Comment 6: More references should be added, which will support your work.
Author Response
Reviewer 1
Comment 1: The title does not sufficiently reflect the objective or content of the report.
Response 1: Thank you for pointing this out. We agree with this comment. Therefore changed the title of the case report on page 1 lines 3 and 4 (title: Genotype-phenotype correlation in a couple in which the wife is a carrier of the beta-thalassemia trait and the husband is a carrier of a mutation in the ALAS2 gene. Both gene defects are associated with non-iron-deficiency microcytic anemia).
Comment 2: The objective needs to be improved.
Response 2: we have reviewed the manuscript and improved it by making changes to: title; figure caption.
Comment 3: The objective and design of the study should be presented at the end of the introduction section.
Response 3: the objective and design of the study were explained in the introductory section from line 19 to line 27 on page 1.
Comment 4: The source of the data used to produce the different figures and tables should be mentioned below the corresponding illustration.
Response 4: the source of the data used, figures and tables were produced by me.
Comment 5: The division of the content into sections should be reviewed and organized, so that the main sections and subsections are clear and distinct and do not interfere.
Response 5: the division of the content of the paper as requested by you and as per the editor's guideline, is organized in: Introduction, detailed description of the case, discussion and conclusion.
Comment 6: More references should be added, which will support your work.
Response 6: as per your indication another reference has been inserted on page 4 and line 124.
Reviewer 2 Report
Comments and Suggestions for AuthorsIn this case report, the authors suggest that, in addition to blood indices and biochemical analysis, genetic testing can also be used to explore and diagnose sideroblastic anaemia. However, there are several major concerns:
1. In Tables 1 and 2, the authors provide the blood indices and biochemical data for the couple and their parents. Could the authors clarify whether these measurements were taken at specific times? Different physiological states might influence the blood indices and biochemical values, which could, in turn, affect the assessment of whether these values are considered normal for the subjects studied.
2. The authors mention the impact of the ALAS2 gene mutation on the mechanism of sideroblastic anaemia. Did the researchers perform next-generation sequencing on these subjects and identify the C>T mutation?
3. Apart from the ALAS2 gene, are there other genetic variants, whether small or large, that may influence sideroblastic anaemia? A more comprehensive review of the literature is recommended to explore the impact of these variants on the phenotype in future studies.
Author Response
Reviewer 2
Comment 1. In Tables 1 and 2, the authors provide the blood indices and biochemical data for the couple and their parents. Could the authors clarify whether these measurements were taken at specific times? Different physiological states might influence the blood indices and biochemical values, which could, in turn, affect the assessment of whether these values are considered normal for the subjects studied.
Response 1: Blood indices and biochemical data were performed on the same day for both the couple and the parents, taking care to exclude external events that could influence the outcome of the analyses.
Comment 2. The authors mention the impact of the ALAS2 gene mutation on the mechanism of sideroblastic anaemia. Did the researchers perform next-generation sequencing on these subjects and identify the C>T mutation?
Response 2: Yes, we performed next-generation sequencing on these subjects.
Comment 3. Apart from the ALAS2 gene, are there other genetic variants, whether small or large, that may influence sideroblastic anaemia? A more comprehensive review of the literature is recommended to explore the impact of these variants on the phenotype in future studies.
Response 3: There are other genes that can influence sideroblastic anemia; but given the husband's clinical history and the remission of anemia with pyridoxine therapy, we decided to study the ALAS2 gene.
Reviewer 3 Report
Comments and Suggestions for AuthorsThe Authors have covered an interesting and important topic, but the abbreviation of its presentation makes it incomprehensible in some parts. The following is a list of comments:
1 1. Lines 17-20 - in the first sentence it is stated that they were both healthy carriers. in line 20 - ‘while her husband was not.’ - what does this information refer to?
2 2. Figure 1 - the description is not very clear. There should be information below the figure about who the pedigree family refers to. In the case of both male and female, the authors refer to the same figure. However, the description in the text is not identical for both spouses.
3 3. It appears in the text that some data are given in the supplementary data, which are not included.
4 4. The results of both genetic and biochemical tests of the spouses (differences between them) should be tabulated, which would be clearer and easier to draw the described conclusions.
Author Response
Reviewer 3
Comment 1.1: Lines 17-20 - in the first sentence it is stated that they were both healthy carriers. in line 20 - ‘while her husband was not.’ - what does this information refer to?
Response 1.1: Thank you for pointing this out. We agree with this comment. therefore we clarified the sentence by modifying the concept in line 20 on page 1. [A biochemical screening performed ten years earlier showed that both spouses were healthy carriers of the beta-thalassemia trait. A careful analysis of the biochemical data and an in-depth molecular diagnosis of the alpha and beta globin genes showed that the woman was a healthy carrier of the beta-thalassemia trait while the husband was a healthy carrier a mutation in the ALAS2 gene.]
Comment 2.2: Figure 1 - the description is not very clear. There should be information below the figure about who the pedigree family refers to. In the case of both male and female, the authors refer to the same figure. However, the description in the text is not identical for both spouses.
Response 2.2: Thank you for pointing this out. We agree with this comment. As you suggested, we have enriched the caption of figure 1, which is on page 2, line 45-46. Figure 1. Pedigree family. Mr. III 1 and III2 came to our observation because Mrs. III2 was pregnant in the first trimester of pregnancy. Molecular family investigation has shown that II2 and III2 are healthy carriers of a mutation in the ALAS2 gene. The ALAS2 gene is located on the short arm of the X chromosome (Xp11.21)
Comment 3.3: It appears in the text that some data are given in the supplementary data, which are not included.
Response 3.3: all clinical, biochemical and genetic data are present in paragraph 2 entitled "Detailed Case Description"
Comment 4 4. The results of both genetic and biochemical tests of the spouses (differences between them) should be tabulated, which would be clearer and easier to draw the described conclusions.
Response 4.4: The results of the genetic and biochemical tests of the spouses (differences between them) are reported in tables 1 and 2 on page 3 of the manuscript.
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsThere are no further suggestions.
