Enchondromatosis (Ollier disease, Maffucci syndrome) is not caused by the PTHR1 mutation p.R150C.

Enchondromatosis (Ollier disease, Maffucci syndrome) is a rare developmental disorder characterized by multiple enchondromas. Not much is known about its molecular genetic background. Recently, an activating mutation in the parathyroid hormone receptor type 1 (PTHR1) gene, c.448C>T (p.R150C), was reported in two of six patients with enchondromatosis. The mutation is thought to result in upregulation of the IHH/PTHrP pathway. This is in contrast to previous studies, showing downregulation of this pathway in other cartilaginous tumors. Therefore, we investigated PTHR1 in enchondromas and chondrosarcomas from 31 enchondromatosis patients from three different European countries, thereby excluding a population bias. PTHR1 protein expression was studied using immunohistochemistry, revealing normal expression. The presence of the described PTHR1 mutation was analyzed, using allele-specific oligonucleotide hybridization confirmed by sequence analysis, in tumors from 26 patients. In addition, 11 patients were screened for other mutations in the PTHR1 gene by sequence analysis. Using both allele-specific oligonucleotide hybridization and sequencing, we could neither confirm the previously found mutation nor find any other mutations in the PTHR1 gene. These results indicate that the PTHR1 gene is not, in contrast to previous suggestions, the culprit for enchondromatosis.