MEN1 gene

Familial isolated hyperparathyroidism

Variants (also called mutations) in the MEN1 gene have been found in some people with familial isolated hyperparathyroidism, a condition characterized by overactive parathyroid glands (hyperparathyroidism). These four glands are located in the neck and release a hormone that helps regulate the levels of calcium in the blood. This regulation is disrupted in people with familial isolated hyperparathyroidism, which can lead to high blood calcium levels (hypercalcemia), kidney stones, thinning of the bones (osteoporosis), nausea, vomiting, high blood pressure (hypertension), weakness, and fatigue.

Many of the variants in the MEN1 gene that are associated with familial isolated hyperparathyroidism cause cells to produce an abnormal form of the menin protein. These abnormal proteins may be shorter than normal, a single protein building block (amino acid) may be substituted for another. It is thought that these amino acid changes impair menin's ability to interact with other proteins. Without functional menin proteins, cells likely divide too frequently, causing one or more of the parathyroid glands to become enlarged (hyperplasia) or to develop a tumor, which is typically noncancerous (benign). Tumors or enlarged parathyroid glands stimulate the overproduction of parathyroid hormone, which triggers the release of calcium into the blood. This excess calcium causes the characteristic features of familial isolated hyperparathyroidism.

Hyperparathyroidism is the most common sign of another condition called multiple endocrine neoplasia type 1 (described below). However, familial isolated hyperparathyroidism is diagnosed in people who do not have the other features of multiple endocrine neoplasia type 1. Researchers speculate that the variants that cause familial isolated hyperparathyroidism have a milder effect on the function of menin than the variants that cause multiple endocrine neoplasia type 1. Occasionally, individuals with familial isolated hyperparathyroidism later develop features of multiple endocrine neoplasia type 1. The cases of familial isolated hyperparathyroidism that are caused by MEN1 gene variants may be an early or mild form of multiple endocrine neoplasia type 1.

Multiple endocrine neoplasia

Over a thousand variants in the MEN1 gene have been found to cause multiple endocrine neoplasia. Multiple endocrine neoplasia typically involves the development of tumors in two or more of the body's hormone-producing glands, called endocrine glands. These tumors can be benign or cancerous. The endocrine glands that are most commonly affected in people with multiple endocrine neoplasia type 1 are the parathyroid glands, the pituitary gland, and the pancreas, although additional endocrine glands and other organs can also be involved. When the condition is caused by MEN1 gene variants, it is known as multiple endocrine neoplasia type 1.

Most of the MEN1 gene variants that are associated with multiple endocrine neoplasia type 1 cause cells to produce an abnormally short, inactive version of menin or an unstable protein that is rapidly broken down. As a result of these variants, one copy of the MEN1 gene in each cell makes no functional protein. If the second copy of the MEN1 gene is also altered, the cell has no working copies of the gene and does not produce any functional menin. For unknown reasons, a second variant occurs most often in the cells of the endocrine glands. Without menin, these cells can divide too frequently and form the tumors that are characteristic of multiple endocrine neoplasia type 1.

Primary macronodular adrenal hyperplasia

MedlinePlus Genetics provides information about Primary macronodular adrenal hyperplasia

Other tumors

Some gene variants, called somatic variants, are acquired during a person's lifetime and are present only in certain cells. Somatic variants in the MEN1 gene have been identified in several types of nonhereditary (sporadic) tumors. Specifically, MEN1 gene variants have been found in a significant percentage of benign tumors of the parathyroid glands (parathyroid adenomas); pancreatic tumors called nonfunctioning neuroendocrine tumors, gastrinomas, and insulinomas; and cancerous tumors of the major airways in the lungs (bronchi) called bronchial carcinoids. Many of these tumor types are also found in people who have multiple endocrine neoplasia type 1. As in people with multiple endocrine neoplasia type 1, tumors occur only when both copies of the MEN1 gene are inactivated in certain cells.