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

Abstract

Communicated by Arnold MunnichEnchondromatosis (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. Hum Mutat 24: [466][467][468][469][470][471][472][473] 2004. r 2004 Wiley-Liss, Inc.

Absence of IHH and retention of PTHrP signalling in enchondromas and central chondrosarcomas

“…Here we demonstrate absence of IHH signalling in two enchondromas and three chondrosarcomas from enchondromatosis patients. In addition, we previously screened 31 patients and could not find any PTHR1 mutations [26]. These data again indicate that PTHR1 is not the culprit for enchondromatosis.…”

Enfermedad de Ollier: tumores benignos con riesgo de malignización. Revisión de 17 casos

“…Es una enfermedad de etiología desconocida con una baja prevalencia 1/100.000 1 y presenta una distribución unilateral en muchos casos, por lo que distintos autores han buscado asociaciones genéticas [2][3][4] .…”

Insights into Enchondroma, Enchondromatosis and the risk of secondary Chondrosarcoma. Review of the literature with an emphasis on the clinical behaviour, radiology, malignant transformation and the follow up

“…[Of the small tubular bones, the metacarpals and metatarsals were less often involved than the phalanges of the hands and feet (n=9 and n=14, respectively)] E = Enchondroma, SE = Solitary Enchondroma, ME = Multiple Enchondromas / Enchondromatosis, MO = multiple Osteochondroma, MS = Maffucci Syndrom, CS = Chondrosarcoma , sSC = secondary Chondrosarcoma, dCS = dedifferentiated Chondrosarcoma Another study group could not confirm this finding of an activating mutation in the parathyroid hormone receptor type 1 (PTHR1) gene. Rozeman et al investigated PTHR1 in enchondromas and chondrosarcomas from 31 enchondromatosis patients from three different European countries, thereby excluding a population bias [36]. PTHR1 protein expression was studied using immunohistochemistry, revealing normal expression.…”

“…PTHR1 protein expression was studied using immunohistochemistry, revealing normal expression. The presence of the described PTHR1 mutation was analyzed, in tumors from 26 patients [36]. In addition, 11 patients were screened for other mutations in the PTHR1 gene by sequence analysis.…”

“…They could neither confirm the previously found mutation nor find any other mutations in the PTHR1 gene. Thus, PTH1R mutations may contribute to the disease in a small subset of Ollier patients but is probably not causative for the disease [36].…”