Genotype-Phenotype Correlations in Neurofibromatosis Type 1: Identification of Novel and Recurrent NF1 Gene Variants and Correlations with Neurocognitive Phenotype

Round 1

Reviewer 1 Report

The authors conducted an interesting study describing neurofibromatosis type 1 mutational spectrum using a robust methodology and genotype-phenotype correlations. The description of novel variants and an attempt to establish genotype-phenotype correlations in Neurofibromatosis type 1 is relevant and very important to understand disease variability and offer better genetic counseling to the patients. I have minor comments to the authors: 

1. I think that the introduction section is long and could be more focused on NF1 genotype-phenotype correlations. 
2. The authors stated that “The classification was conducted in accordance with the guidelines from the American College of Medical Genetics and Genomics”. However, this guideline does not have a category named “unknown significance”. Additionally, please provide reference and version of the American College of Medical Genetics and Genomics guidelines used. 
3. Please provide more details about statistical analysis – patients with the same type of mutations were grouped in each of the clinical groups (G1, G2..)?
4. In the results section, please provide the average depth, depth of the identified variants and minimum and maximum depth obtained in NGS in each sample.
5. The authors could briefly discuss the influence of variants in other genes in NF1 phenotype, which has been investigated in scientific studies. 
6. The authors could discuss the limitations of their study, including the small number of patients in each clinical group.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Please see the attached review.

Comments for author File: Comments.pdf

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

In my opinion the Authors significantly improved the manuscript. However, there are still some issues that need to be addressed. 

Please see the attached review.

Comments for author File: Comments.pdf

Author Response

Please see the attachment.

Author Response File: Author Response.pdf