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Genetic developments in Hypoparathyroidism

2001; Elsevier BV; Volume: 357; Issue: 9261 Linguagem: Inglês

10.1016/s0140-6736(00)04254-9

1474-547X

Rajesh V. Thakker,

Growth Hormone and Insulin-like Growth Factors

Molecular genetic studies are throwing light on the pathogenesis of the hypoparathyroid disorders, 1 Bilezikian JP Thakker RV Hypoparathyroidism. Curr Opin Endocrinol Diabetes. 1998; 4: 427-432 Crossref Scopus (8) Google Scholar which may be classified according to whether they arise from a deficiency of parathyroid hormone (PTH), a defect in the PTH-receptor (ie, the PTH/PTHrP receptor), or an insensitivity to PTH caused by defects downstream of the PTH/PTHrP receptor (figure). These studies have also thrown light on some of the mechanisms regulating parathyroid-gland development, PTH secretion, and PTH-mediated actions in target tissues. Thus, mutations in the gene encoding the calcium-sensing receptor (CaSR) have been reported in patients with autosomal dominant hypocalcaemia with hypercalciuria, a disorder associated with an inappropriately low PTH. In addition, mutations in the PTH gene, the transcriptional factors GCM2 and GATA3, and the mitochondrial genome have been associated with PTH deficiency; defects in the PTH/PTHrP receptor gene, which impair its function, have been identified in patients with Blomstrand's lethal chondrodysplasia, which is probably associated with hypocalcaemia; and inactivating mutations in the stimulatory G protein (Gsα) have been found in individuals with pseudohypoparathyroidism type Ia and pseudopseudohypoparathyroidism. 1 Bilezikian JP Thakker RV Hypoparathyroidism. Curr Opin Endocrinol Diabetes. 1998; 4: 427-432 Crossref Scopus (8) Google Scholar Furthermore, the gene causing the polyglandular autoimmune syndrome (APECED) has been characterised, and candidate genes have been identified for DiGeorge syndrome and for pseudohypoparathyroidism type Ib.