Gigantism, acromegaly, and GPR101 mutations.

To the Editor: Trivellin et al. (Dec. 18 issue)1 report a recurrent activating GPR101 mutation (p.E308D) in 11 of 248 tumor DNA samples from patients with isolated acromegaly. Of these patients, 3 carried a germline GPR101 mutation. Two of the 3 patients are being treated at our institution and were identified among 38 patients from our cohort. This might suggest a higher prevalence of germline GPR101 mutation among French patients with sporadic acromegaly. We therefore screened our entire cohort of 263 patients with gigantism or acromegaly for germline mutations in GPR101, which encodes a G-protein–coupled receptor, and in AIP, which encodes aryl hydrocarbon receptor–interacting protein (Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Only 3 patients (1.1%), including the 2 patients who were reported previously, had the GPR101 p.E308D mutation; all 3 of these patients had adult-onset sporadic acromegaly. This finding shows that the prevalence of this germline mutation in our large cohort is very similar to that reported by Trivellin et al. In addition, we identified in a patient with sporadic acromegaly a novel GPR101 p.D366E variant (0.4%), which was not reported in the databases of the Exome Aggregation Consortium (ExAC), 1000 Genomes Project, dbSNP, or Exome Variant Server. Germline AIP mutations were identified in 8 of 263 patients with somatotropinomas (3.0%), of whom 6 patients (75%) have gigantism.2 None of the 263 patients carried germline mutations in both GPR101 and AIP.