Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP)

Germline and de novo mutations in the HRPT2 tumour suppressor gene in familial isolated hyperparathyroidism (FIHP) N We were able to document that L64P had occurred de novo in an affected woman who carried the mutation in a somatic and germline mosaic state.The other five FIHP kindreds were negative for germline mutations in all three genes identified for FIHP, HRPT2, MEN1, and CASR. NIn conclusion, we demonstrate that HRPT2 is a disease gene for 1q linked FIHP and underline the possibility of mutations occurring de novo in this gene.The results further support that a subset of FIHP is a variant of HPT-JT, which has implications for clinical diagnostic purposes and for improved understanding of parathyroid tumour development.