To the Editors:

We thank Drs. Machens and Dralle for reviewing our paper so thoroughly and pointing out some potential problems with our Table 3. Specifically, they have raised the question of whether there could have been overlap in some of the studies we included that reported C609G and C609S RET mutations. It does appear plausible that three of the five reports of C609S mutations could have overlap, as they all originate from Semmelweis University in Budapest.1–3 Although there are discrepancies between these three reports, such as the age of one affected person with pheochromocytoma, and whether there are two or three family members with medullary thyroid cancer (MTC), it seems reasonable to suspect that these studies are discussing the same family. Combining this C609S family with that described by Kinlaw et al. and the recent report by Mian et al., 6/29 (21%) affected family members had pheochromocytoma, and the youngest case of MTC was found at an age of 17 years.4,5

Similarly, the reports of two families described with C609G RET mutations by Simon et al. and Fitze et al. both share one author from Erlangen, and their pedigrees are similar enough to suggest they also represent a single family.6,7 We therefore agree that the numbers represented in our Table 3 for C609S and C609G mutations overestimate the prevalence of pheochromocytoma in families with these mutations. However, this prevalence is still higher than for any other mutations in RET codon 609, and the youngest ages of the diagnosis of MTC were also earlier (age 5 years for C609G and 17 years for C609S). The evidence therefore supports our original conclusion that C609G and C609S mutations are associated with more aggressive disease.