Molecular genetics of parathyroid disease

Recent advances in molecular biology and cytogenetics have made it possible to localize, clone, and characterize some of the genetic abnormalities that result in parathyroid diseases. Thus mutations in the recently cloned calcium-sensing receptor gene have been reported in patients with familial benign hypercalcemia and autosomal dominant hypocalcemia, and the role of PRAD1 has revealed a novel cyclin to be involved in the pathogenesis of some parathyroid tumors. In addition, muta-tions in the parathyroid hormone gene and the mitochondrial genome have been demonstrated to be associated with some forms of hypoparathyroidism, and mutations in the Gsαgene have been demonstrated in some patients with pseudohypoparathyroidism. Candidate genes for the DiGeorge syndrome have also been identified. The locations of other susceptibility genes, eg, multiple endocrine neoplasia type 1 and the hereditary hyperparathyroidism and jaw tumor syndromes have been identified on chromosomes 11q13 and 1q21-q31, respectively, and genetic heterogeneity in the familial benign hypercalcemia and DiGeorge disorders has been established. These molecular genetic studies have provided a unique opportunity to elucidate the pathogenesis of some diseases of the parathyroids.