ClinVar

Among the 13 different heterozygous germline inactivating mutations in the HRPT2 gene found in 14 families with hyperparathyroidism-jaw tumor syndrome (HRPT2; 145001) by Carpten et al. (2002), there was only 1 recurrent mutation, 679insAG in exon 7, causing a frameshift. This mutation was found in 2 independently identified, seemingly unrelated families who were later found to share an identical disease haplotype through the entire 26-marker interval, suggesting that these individuals had a common ancestor.

In a direct sequencing study of 21 parathyroid carcinomas from 15 patients who had no known family history of primary hyperparathyroidism (HRPT1; 145000) or the HPT-JT syndrome at presentation, Shattuck et al. (2003) found a germline 679insAG mutation and a tumor-specific somatic HRPT2 mutation in the other allele (Y54X; 607393.0008). The insertion was in exon 7 and was predicted to cause a frameshift at amino acid 227 with a stop codon at 257.

Simonds et al. (2004) 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 (131100), hypocalciuric hypercalcemia (145980), and HPT-JT and negative mutational screening of MEN1 and the gene encoding the calcium-sensing receptor (CASR; 601199). The families were characterized by young probands (42 +/- 3 years) and occasionally unusual parathyroid histology, including 4 families with 1 case of parathyroid cancer. Among the 32 FIHP families, only a single one was found to have a mutation in HRPT2 (679insAG); this mutation predicts premature termination of its gene product, parafibromin, and thus its presumed inactivation.