Familial Isolated Hyperparathyroidism Is Rarely Caused by Germline Mutation inHRPT2, the Gene for the Hyperparathyroidism-Jaw Tumor Syndrome

Publisher Website
Google Scholar
Abstract
Familial isolated hyperparathyroidism (FIHP) can result oc- casionally from the incomplete expression of a syndromic form of familial hyperparathyroidism (HPT), specifically mul- tiple endocrine neoplasia type 1 (MEN1), familial hypocalci- uric hypercalcemia, or the hyperparathyroidism-jaw tumor syndrome (HPT-JT). The cause of FIHP has not been identi- fied in the majority of families. We investigated 32 families with FIHP to determine the frequency of occult mutation in HRPT2, the gene causing HPT-JT. All families had negative clinical testing for MEN1, hypocalciuric hypercalcemia, and HPT-JT and negative mutational screening of MEN1 and CASR, the gene for the calcium-sensing receptor. Thus, an extended effort was made to exclude each of the principal syndromic causes of FIHP. The families were characterized by young probands (42 3 yr) and occasionally unusual para- thyroid histology, including four families with one case of parathyroid cancer. We had speculated that there was a high frequency of occult mutation in HRPT2 among such carefully screened kindreds. This hypothesis became testable with the recent identification of that gene. Among the 32 FIHP families, only a single one was found to have a mutation in HRPT2 (679insAG); this mutation predicts premature truncation of its gene product, parafibromin, and thus its presumed inac- tivation. Even accounting for families with one of the three occult syndromes and false negative biochemical or DNA test- ing, these results indicate that an unexpectedly large fraction of FIHP has currently unrecognized causes. (J Clin Endocri- nol Metab 89: 96 -102, 2004)

This publication has 0 references indexed in Scilit: