Back to Search
Start Over
Genetic Analyses of theHRPT2Gene in Primary Hyperparathyroidism: Germline and Somatic Mutations in Familial and Sporadic Parathyroid Tumors
- Source :
- The Journal of Clinical Endocrinology & Metabolism. 89:5583-5591
- Publication Year :
- 2004
- Publisher :
- The Endocrine Society, 2004.
-
Abstract
- We investigated the involvement of the HRPT2 gene by loss of heterozygosity analysis and direct sequencing in a kindred with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and three kindreds with familial isolated primary hyperparathyroidism (FIHP). Seven patients with sporadic parathyroid cancers and 35 with parathyroid adenomas with no family history of primary hyperparathyroidism or HPT-JT were also studied. A germline heterozygous substitution G to A was found in the donor splice site of intron 1 in one of the three FIHP families. No mutations were identified in the HPT-JT kindred. A somatic HRPT2 mutation was found in four of seven patients with parathyroid cancers, two of which were unreported frameshift mutations (195insT and 195insA) in exon 2. Consistent with recent findings, two of seven patients with sporadic parathyroid cancer had germline mutations. Four adenomas showed loss of heterozygosity at HRPT2, whereas a somatic HRPT2 mutation was found in one. In conclusion, we provide additional evidence for a strong association between HRPT2 gene mutations and sporadic parathyroid cancer. The finding that two of the seven patients with sporadic parathyroid cancer carried an HRPT2 germline mutation suggests that they might have occult HPT-JT. Our results also confirm the need for testing HRPT2 gene in FIHP families.
- Subjects :
- Adenoma
Adult
Male
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
Loss of Heterozygosity
Biology
Biochemistry
Loss of heterozygosity
Endocrinology
Germline mutation
Internal medicine
medicine
Humans
Germ-Line Mutation
Parathyroid adenoma
Genetics
Hyperparathyroidism
Parathyroid neoplasm
Tumor Suppressor Proteins
Biochemistry (medical)
Proteins
Middle Aged
medicine.disease
Hyperparathyroidism-Jaw Tumor Syndrome
Parathyroid Neoplasms
Parathyroid carcinoma
Female
Primary hyperparathyroidism
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 89
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....04fc82df7831beb1175989543aba0e2a