Congenital Hypopigmentary Disorders with Multiorgan Impairment: A Case Report and an Overview on Gray Hair Syndromes

Round 1

Reviewer 1 Report

Good presentation and summary of existing studies and case reports. Good presentation of investigations and findings.

Author Response

Response to Reviewer 1 Comments

 We would be honored to resubmit to Medicina the revised manuscript entitled “Congenital Hypopigmentary Disorders With Multi-Organ Impairment: A Case Report And An Overview On Gray Hair Syndromes”

Hereinafter, we provide a point-by-point response letter.

Point 1: English language and style are fine/minor spell check required.

Good presentation and summary of existing studies and case reports. Good presentation of investigations and findings.

 

Response 1: We changed the text as you suggested. English language and style of the manuscript has been completely revised. We have corrected all grammar and spelling errors.

Author Response File: Author Response.doc

Reviewer 2 Report

Overall this is a good story, in Figure 2, I would suggest the authors to use a black hair as a control for a better presentation.

Author Response

We would be honored to resubmit to Medicina the revised manuscript entitled “Congenital Hypopigmentary Disorders With Multi-Organ Impairment: A Case Report And An Overview On Gray Hair Syndromes”

Hereinafter, we provide a point-by-point response letter.

Point 1: English language and style are fine/minor spell check required.

 

Response 1: We changed the text as you suggested. English language and style of the manuscript has been completely revised. We have corrected all grammar and spelling errors.

 

Point 2: Overall this is a good story, in Figure 2, I would suggest the authors to use a black hair as a control for a better presentation.

 

Response 2: As you suggested, we added in Figure 2 the images of a human hair from a healthy Caucasian individual. In fact, the morphological abnormalities of the GS patients' hair is now much clearer.

 

Author Response File: Author Response.doc

Reviewer 3 Report

The authors have adequately captured all the elements of a case report in this manuscript and described the gray hair syndromes adequately.

Author Response

We would be honored to resubmit to Medicina the revised manuscript entitled “Congenital Hypopigmentary Disorders With Multi-Organ Impairment: A Case Report And An Overview On Gray Hair Syndromes”

Hereinafter, we provide a point-by-point response letter.

Point 1: English language and style are fine/minor spell check required.

The authors have adequately captured all the elements of a case report in this manuscript and described the gray hair syndromes adequately.

 

Response 1: We changed the text as you suggested. English language and style of the manuscript has been completely revised. We have corrected all grammar and spelling errors.

Author Response File: Author Response.doc

Reviewer 4 Report

Comments to Authors:

This manuscript is entitled “Congenital Hypopigmentary Disorders with Multi-Organ Impairment: A Case Report and an Overview on Gray Hair Syndromes” that is a case report of Griscelli syndrome type 2 with a canonical splice site mutation in intron 5 of RAB27A gene. You are definitively right that with a highly heterogeneous heritable group of disorders that “identifying the pathogenic mutations is mandatory to reach diagnostic certainty”. While the manuscript is well written and provides valuable information for the physicians to manage the patients affected by these heterogeneous groups of disorders, I have some amendments/comments for improvement.

1- The rows and columns of the table (Table 1. Clinical and genetic findings of Gray Hair Syndromes) is out of order and it is hard to follow the second column related to the rows. Please correct it accordingly. In addition, there is an explanation of just LYST gene in the table but no other gene (“LYST mutations cause impairment of lysosomes function in a wide range of cells, such as immune system cells…”). Since you mention the gene function in the text, it may be better to remove it from the table.

2- Page 1, line 34: it should be “...clinically identifiable since the first week of life…” instead of “…clinically identifiable since the first weeks of life;

3- Page 1, line 44: it should be “…. all known GHS to date.” instead of “all GHS know to date”.

4- Since the sentence on page 4 line 57 and 58 is confusing and not clear, please rephrase it “The 37 years-old father reported very light blond body and scalp hair before developing, 15 years earlier, severe alopecia universal”.

5- Page 5, line 86, Figure legend 3: the gene should be in italic “The five coding exons of RAB27A gene…”

6- All abbreviations are spelled out except CHD. Page 6, line 102: Please spell out CHD.

7- Just as a suggestion for future follow-up, it would be great if the authors do RNA-Seq (whole transcriptome study) on the patient to see the consequences of the mutation on the transcript of RAB27A gene. Since it is a germline recessive mutation, it will be applicable to do RNA-Seq from a whole blood sample.

Author Response

We would be honored to resubmit to Medicina the revised manuscript entitled “Congenital Hypopigmentary Disorders With Multi-Organ Impairment: A Case Report And An Overview On Gray Hair Syndromes”

Hereinafter, we provide a point-by-point response letter.

This manuscript is entitled “Congenital Hypopigmentary Disorders with Multi-Organ Impairment: A Case Report and an Overview on Gray Hair Syndromes” that is a case report of Griscelli syndrome type 2 with a canonical splice site mutation in intron 5 of RAB27A gene. You are definitively right that with a highly heterogeneous heritable group of disorders that “identifying the pathogenic mutations is mandatory to reach diagnostic certainty”. While the manuscript is well written and provides valuable information for the physicians to manage the patients affected by these heterogeneous groups of disorders, I have some amendments/comments for improvement.

Point 1: English language and style are fine/minor spell check required.

 

Response 1: We changed the text as you suggested. English language and style of the manuscript has been completely revised. We have corrected all grammar and spelling errors.

 

Point 2: The rows and columns of the table (Table 1. Clinical and genetic findings of Gray Hair Syndromes) is out of order and it is hard to follow the second column related to the rows. Please correct it accordingly. In addition, there is an explanation of just LYST gene in the table but no other gene (“LYST mutations cause impairment of lysosomes function in a wide range of cells, such as immune system cells…”). Since you mention the gene function in the text, it may be better to remove it from the table

 

Response 2: We modified Table 1 as you suggested, making it easier to read. We also removed the sentence “LYST mutations cause…”, which was already reported in the text.

 

Point 3: Page 1, line 34: it should be “...clinically identifiable since the first week of life…” instead of “…clinically identifiable since the first weeks of life;

 

Response 3: We changed the text as you suggested.

 

Point 4: Page 1, line 44: it should be “…. all known GHS to date.” instead of “all GHS know to date”.

 

Response 4: We changed the text as you suggested.

 

Point 5: Since the sentence on page 4 line 57 and 58 is confusing and not clear, please rephrase it “The 37 years-old father reported very light blond body and scalp hair before developing, 15 years earlier, severe alopecia universal”.

 

Response 5: We have reformulated the sentence.

 

Point 6: Page 5, line 86, Figure legend 3: the gene should be in italic “The five coding exons of RAB27A gene…”

 

Response 6: We changed the text as you suggested.

 

Point 7: All abbreviations are spelled out except CHD. Page 6, line 102: Please spell out CHD.

 

Response 7: We spelled out CHD (Congenital Pigmentary Disorders) at Page 1 Line 31.

 

Point 8: Just as a suggestion for future follow-up, it would be great if the authors do RNA-Seq (whole transcriptome study) on the patient to see the consequences of the mutation on the transcript of RAB27A gene. Since it is a germline recessive mutation, it will be applicable to do RNA-Seq from a whole blood sample.

 

Response 8: We thank you very much for the interesting suggestion.

In accordance with the Standards and guidelines of the American College of Medical Genetics, the homozygous mutation found in our proband had a very strong evidence of pathogenicity. In this regard, we have added the corresponding reference ([12]).

The same mutation in a heterozygous state was confirmed in both parents. Moreover, the clinical features of our patient correspond perfectly to the typical phenotype of GS, type 2. We added in the text your observation: Page 6, line 101-103 Figure 3 Legend “The cDNA analysis from total RNA isolated from pre-transplantation bone marrow of the proband or from the parents’ peripheral blood sample could define the effect of germline mutations of RAB27A gene on its transcription”.

 

Author Response File: Author Response.doc