Diseases of mineral metabolism such as familial multiple endocrine neoplasia type 1 (FMEN1),
familial hypocaliuric hypercalcemia (FHH), familial hyperparathyroidism (FH), and
pseudohypoparathyroidism (PHP) are known as hereditary abnormalities. Meaning these
conditions are passed from parents to their children through genes. These specific conditions
result in abnormal levels of calcium in the blood.
This study was designed to help researchers understand more about the genes that are
responsible for these disorders. By learning more about the genetic process involved in
hereditary abnormalities, new tests and treatments can be developed.
Subjects for this study will be members of families that have had relatives diagnosed with a
disease of mineral metabolism. Participants will be asked to give blood samples for DNA
extraction. DNA is the part of cells that carries genetic information.
The DNA will be analyzed and the results given to the subjects. Genetic counseling will be
provided to subjects to aid in interpreting their results.
Familial multiple endocrine neoplasia type 1 (MEN1), familial hypocalciuric (or familial
benign) hypercalcemia (FHH), hyperparathyroidism jaw tumor syndrome (HPT-JT), other causes of
familial isolated hyperparathyroidism (FIH), and pseudohypoparathyroidism (PHP) are disorders
of metabolism that are generally inherited in an autosomal dominant fashion. MEN1 is
characterized by overgrowth and hyperfunction of the parathyroids, anterior pituitary and
gastrointestinal endocrine tissue. MEN1, p15, p18, p21, and p27 are identified genes for MEN
1- like states. FHH is characterized by a usually benign syndrome sometimes mistaken for
typical primary hyperparathyroidism, which may result in unnecessary and unsuccessful
parathyroid surgery. The CASR gene for the calcium-sensing receptor of the parathyroid cell
is mutated in of most FHH kindreds;a minority of kindreds with FHH have mutation of the GA11
or AP2S gene. HPT-JT is a distinctive subtype of familial isolated hyperparathyroidism that
has combinations of parathyroid adenoma, parathyroid cancer, jaw tumor, uterus tumor, kidney
tumor and kidney cysts. It is caused by mutation of the HRPT2 gene. PHP is characterized by
parathyroid hormone resistance, and one form is associated with mutations in the gene
encoding the stimulatory G protein. We are continuing to collect blood and tissue samples
from affected and unaffected members of kindreds with known or suspected MEN1, FHH, HPT-JT,
FIH, PHP, and related disorders for the purpose of genetic analysis and gene identification.
In most cases, the procurement of specimens will be at an off-site location. Samples will be
processed for extraction of DNA and RNA.
- INCLUSION CRITERIA
Patients with known or suspected metabolic disorders of such as MEN 1, MEN 1-like states,
FHH, HPT-JT, FIH, FIC, PHP and their first degree relatives (parents, siblings and
offspring) and spouses. For the most part only one index case in a family will be tested.
Pre-test counseling by an NIDDK investigator.