First of all, thank you for your interest and your critical comments on our article.

The main goal of our work was to compare several aspects of a gene network based on phenotypic similarity with inferred networks of diseasomes built from data available in OMIM and Orphanet. We are aware that some disease contained in Orphanet database do not fit with current definition of rare disease, and even some of them corresponde to common diseases, which does not override Orphanet as a valuable repository of genetic diseases. In fact, Orphanet follows a system to classify diseases that is reviewed by expert clinicians and that differs significantly from OMIM, which means that it can be taken as an alternative soure of information with great interest for the kind of study we carried out.
Please, note that the prevalence of diseases was not a subject of study in our article.
It is true that in the section "Enrichment of essential genes in the pleiotropic subsets", we made an evaluation of the enrichment of esential genes and its possible relationship with prevalence concerning the observations and comparison made by Zhang et al (2011) [reference 11 in our article]. Our resuts with the dataset of Orphanet associated genes seem to fit well with those shown in reference 11. On the other hand, the percentage of essential genes contained in OMIM diseases reported in reference 11 seems to be underestimated and does not fit well wht that previously calculated by Goh et al (2007) [reference 10 in our article]. In Reference 11 this percentage was calculated taking into account "the entire set of OMIM disease genes (Morbid Map of the OMIM database)", obtaining 3864 genes associated to disease, which afterwards were subdivided in OMGD and NOMGD. Among those genes that were taken into account in Reference 11, there is a number of them for which the causal molecular bases remain unknown. Certainly, for such diseases genetic analysis does not allow to confirm gene-disease associations. In our study, we followed strictly the criteria used in Reference 10 to generate an updated version (as of the second half of 2012) of the dataset used in your work in Reference 11. In our case, this yielded a list of 2525 genes, including a 33.9% of essential genes.

We agree with you in considering an interesting topic to be studied the possible relationship between gene disease prevalence and the features of their associated genes. However, as you will be aware, the accurate use of the concept prevalence involves a number of issues and difficulties. Among others: (1) The concept "rare disease" is not defined unambiguously, since the used threshold prevalence value varies among countries. (2) Prevalence values can vary widely in many instances. In fact, some diseases are very rare for some populations/races but frequent for others. (3) Available prevalence data offer only approximate values and there is not variability in the quantitative range to allow the study of clear differences.
On the other hand, since genomic and personalized medicine is centered in the study of individual patients, it is expected that prevalence will become less and less taken into account.

Finally, we are aware that Supplementary Tables S2 contains a number of diseases that are not rare or even are common, as the examples you mention. This is a reflection of what is actually contained in Orphanet. But, please, note that -as mentioned above- the prevalence of diseases was not a subject of study in our article. We would like to underscore that our article rethinks the terms with which diseases are conceptually defined to be studied by a network approach.