Large deletion at the gene locus and search for predictive markers of the presence of a genetic lesion.

The Hyperparathyroidism with Jaw-Tumours syndrome is caused by mutations of the gene: it has been suggested that early onset of the disease and high Ca levels may predict the presence of a mutation. We searched for large deletions at the locus in patients with: HPT-JT (nr 2), atypical adenoma (nr 7) or sporadic parathyroid carcinoma (nr 11) with a specific MLPA and qRT-PCR assays applied on DNA extracted from whole blood. A Medline search in database for all the papers reporting a gene mutation, clinical/histological diagnosis, age at onset, Ca, PTH levels for familial/sporadic cases was conducted with the aim to possibly identify biochemical/clinical markers predictive, in first diagnosis, of the presence of a gene mutation.

Autosomal Dominant PTH Gene Signal Sequence Mutation in a Family With Familial Isolated Hypoparathyroidism.

Context: Familial isolated hypoparathyroidism (FIH) is a genetically heterogeneous disorder due to mutations of the calcium-sensing receptor (CASR), glial cells missing-2 (GCM2), guanine nucleotide binding protein α11 (GNA11), or parathyroid hormone (PTH) genes. Thus far, only four cases with homozygous and two cases with heterozygous mutations in the PTH gene have been reported.

Objective: To clinically describe an FIH family and identify and characterize the causal gene mutation.

Large intragenic deletion of CDC73 (exons 4-10) in a three-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family.

Background: Inactivating mutations of CDC73 cause Hyperparathyroidism-Jaw Tumour syndrome (HPT-JT), Familial Isolated Hyperparathyroidism (FIHP) and sporadic parathyroid carcinoma. We conducted CDC73 mutation analysis in an HPT-JT family and confirm carrier status of the proband's daughter.

Methods: The proband had primary hyperparathyroidism (parathyroid carcinoma) and uterine leiomyomata.

Vitamin D status in primary hyperparathyroidism: effect of genetic background.

Primary hyperparathyroidism (PHPT) is associated with hypovitaminosis D as assessed by serum total 25-hydroxyvitamin D (TotalD) levels. The aim of this study is to evaluate whether this is also the case for the calculated bioavailable 25-hydroxyvitamin D (BioD) or free 25-hydroxyvitamin D (FreeD), and whether the vitamin D status is influenced by genetic background. We compared vitamin D status of 88 PHPT patients each with a matched healthy family member sharing genetic background, i.

A novel mutation in calcium-sensing receptor gene associated to hypercalcemia and hypercalciuria.

Background: Familial Hyperparathyroidism (HPT) and Familial benign Hypocalciuric Hypercalcemia (FHH) are the most common causes of hereditary hypercalcemia. FHH has been demonstrated to be caused by inactivating mutations of calcium-sensing receptor (CaSR) gene, involved in PTH regulation as well as in renal calcium excretion.

Case Presentation: In two individuals, father and son, we found a novel heterozygous mutation in CaSR gene.

Calcium-sensing-related gene mutations in hypercalcaemic hypocalciuric patients as differential diagnosis from primary hyperparathyroidism: detection of two novel inactivating mutations in an Italian population.

Background: Inactivating mutations of the calcium-sensing receptor (CaSR), of the G-protein subunit α11 (GNA11) and of the adaptor-related protein complex 2, sigma 1 subunit (AP2S1) genes are responsible for familial hypocalciuric hypercalcaemia (FHH). The aim of this study was to analyse prevalence and pathogenicity of CaSR, GNA11 and AP2S1 mutations in patients with an FHH phenotype and to compare them with a sample of patients with primary hyperparathyroidism (PHPT) in order to identify the most useful laboratory parameter for a differential diagnosis.

Methods: Patients with an FHH phenotype were studied with polymerase chain reaction amplification and direct sequencing of the entire CaSR, GNA11 and AP2S1 coding sequences.

Identification and functional characterization of three NoLS (nucleolar localisation signals) mutations of the CDC73 gene.

Hyperparathyroidism Jaw-Tumour Syndrome (HPT-JT) is characterized by primary hyperparathyroidism (PHPT), maxillary/mandible ossifying fibromas and by parathyroid carcinoma in 15% of cases. Inactivating mutations of the tumour suppressor CDC73/HRPT2 gene have been found in HPT-JT patients and also as genetic determinants of sporadic parathyroid carcinoma/atypical adenomas and, rarely, typical adenomas, in familial PHPT. Here we report the genetic and molecular analysis of the CDC73/HRPT2 gene in three patients affected by PHPT due to atypical and typical parathyroid adenomas, in one case belonging to familial PHPT.

20 novel point mutations and one large deletion in EXT1 and EXT2 genes: report of diagnostic screening in a large Italian cohort of patients affected by hereditary multiple exostosis.

Background: Hereditary multiple exostosis represents the most frequent bone tumor disease in humans. It consists of cartilage deformities affecting the juxta-ephyseal region of long bones. Usually benign, exostosis could degenerate in malignant chondrosarcoma form in less than 5% of the cases.

CDC73 mutations and parafibromin immunohistochemistry in parathyroid tumors: clinical correlations in a single-centre patient cohort.

Objective: To determine if molecular and immunohistochemical (IHC) features of the HRPT2/CDC73 gene and its product, parafibromin, predict the natural history of parathyroid malignancy, particularly atypical adenoma, as seen in a single-centre patient cohort.

Methods: Matched tumor and non-tumor tissues were obtained from 46 patients with parathyroid carcinoma (CA) (n = 15), atypical adenoma (AA) (n = 14) and typical adenoma (TA) (n = 17), as defined by standardized histopathological criteria. Exons and exon-intron boundaries of the CDC73 gene were sequenced to identify germline or somatic mutations.

CASR gene activating mutations in two families with autosomal dominant hypocalcemia.

Background: Autosomal dominant hypocalcemia (ADH) is an endocrine disorder caused by activating mutations of the calcium-sensing receptor (CASR) gene which plays a major role in maintaining calcium homeostasis. Biochemical features of ADH are hypocalcemia and hypercalciuria with inappropriately low levels of parathyroid hormone (PTH). We report on two four-generation families affected by ADH.

Development of real-time quantitative reverse transcription-PCR for Her2 detection in peripheral blood from patients with breast cancer.

Background: Amplification of the Her2neu oncogene is a well known indicator of poor prognosis in breast cancer patients. The implementation into the clinical setting of therapeutical strategies directly targeting the Her2neu gene product, has create the need for the development of non-invasive analytical techniques in order to monitoring minimal residual disease and response to the treatment.

Methods: To detect the expression of Her2neu mRNA in peripheral blood, we developed a specific real-time quantitative reverse transcription-PCR (QPCR) assay.

Spectrum of PTCH mutations in Italian nevoid basal cell-carcinoma syndrome patients: identification of thirteen novel alleles.

The nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant genetic disease characterized by numerous basal cell carcinomas, odontogenic keratocysts of the jaws, palmar and plantal pits, skeletal abnormalities, and calcification of the falx cerebri. The gene responsible for this syndrome is the PTCH tumor suppressor gene encoding for the sonic hedgehog receptor. In this paper, we report thirteen novel mutations identified in the first screening of NBCCS patients in Italy.