Identification of Germinal Neurofibromin Hotspots
, MarÃa Isidoro-GarcÃa 2,4,5,6, Jesus Lacal 2,3,* and Juan Carlos Triviño 1
Round 1
Reviewer 1 Report
The study by Lois et al examined 2365 known NF1 germline mutations from ClinVar database. This was done by using a binomial and sliding windows test to investigate the association of exon-level mutations with clinical phenotype to improve NF1 genotype-phenotype prediction. Furthermore, the GRD, CSRD, TBD and Armadillo1 domains were identified as putative regions of mutation hotspots. Unfortunately, I am not an expert of the prediction tests used however, from a clinical point of view, I would support the publication of the article. Overall, the manuscript is very well written, with a very detailed introduction that shares all the necessary information with the reader. The results are well described and the figures are comprehensible. The discussion is supported with adequate references. Therefore, I would recommend the manuscript for acceptance.
Reviewer 2 Report
In the manuscript entitled “Identification of Germinal Neurofibromin Hotspots” the Authors have analyzed the distribution of 4610 germinal variants of the NF1 gene from the ClinVar database. Based on the analysis, potential functional neurofibromin hotspots enriched in pathological variants were identified. The results of the study are interesting. In my opinion, the study is generally well written and can be published after editorial corrections.
