We report on the utilisation of a non-consensus (non-canonical) donor splice site within exon 1 of the HRPT2 gene in familial isolated primary hyperparathyroidism (FIHP).
Germline mutations of the MEN1 gene have been reported in some with FIHP, but familial pituitary adenoma usually lacks the MEN1 mutation and has been described as a genetically distinct disorder.
This finding emphasizes that qPCR should be implemented in HRPT2 molecular analysis, which may improve genetic assessment and clinical management of patients with FIHP and HPT-JT.
Parafibromin is a tumor suppressor protein encoded by HRPT2, a gene recently implicated in the hereditary hyperparathyroidism-jaw tumor syndrome, parathyroid cancer, and a subset of kindreds with familial isolated hyperparathyroidism.
FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT).
A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas.
FIHP phenotypes have been associated with mutant MEN1 and calcium-sensing receptor (CASR) genotypes and, very recently, with mutation in the newly identified HRPT2 gene.
The LOH study showed a loss of the wild-type allele, which confirmed that a functional defect of the MEN1 gene product, menin, is etiological for FIHP.
In the present study, we describe two unrelated Italian kindreds with FIHP, in which the clinical, histopathological and genetic analyses of the MEN1 gene and HPRT2 locus at 1q21-32 suggest that both might be a variant of MEN1 and HPT-JT syndromes.
We present three siblings with familial isolated hyperparathyroidism due to solitary parathyroid adenoma and favorable evolution post-parathyroidectomy.Genetic tests revealed HRPT2 mutation.
The entire coding region of the MEN1 gene was sequenced, and mutations were detected in 11 MEN 1 families; one sporadic MEN 1 patient, one case of FIHPT and one MEN 1-like case.
Parafibromin is a tumor suppressor protein encoded by HRPT2, a gene recently implicated in the hereditary hyperparathyroidism-jaw tumor syndrome, parathyroid cancer, and a subset of kindreds with familial isolated hyperparathyroidism.
We report a patient and 11 family members with FIHP in whom we identified a heterozygous G-to-A mutation at nucleotide 7361 of tumor suppressor MEN1 gene.