Fig. 1(A) Primary sequence of human parathyroid hormone (PTH) and organization of its domains. The pre- (signal sequence), pro- (black box), and mature regions (boxed) of PTH are labeled. The first six amino acids in the signal sequence are deleted in a patient with hypoparathyroidism. The arrowheads indicate the wild-type amino acids in pre-pro-PTH that are replaced by mutant amino acids or terminated. (B) Schematic presentation of the human parathyroid hormone (PTH) gene, which consists of three exons and two introns. The G to C nucleotide change at the beginning of intron 2 results in exon 2 being skipped in patients with autosomal dominant familial hypoparathyroidism; [reference], see references for details [8].
Fig. 2(A) Illustration of parathyroid hormone (PTH) synthesis and secretion from chief cells of parathyroid glands. In each step, pathophysiological explanations are noted with x mark. (B) Signal transduction pathways from the activated PTH receptor from its respective target tissues, i.e., bone and kidney. Note that differences in signal transduction pathways activated by either wild type PTH or Cys25PTH(1-84) are still to be investigated. Adapted from Hammer et al. [17], with permission from McGraw-Hill Education. CaR, calcium-sensing receptor; AC adenylate cyclase; PTH-R, PTH receptor; G, G protein; Gs, Gs alpha subunit; PLC, phospholipase C; PIP2, phosphatidylinositol 4,5-bisphosphate; ATP, adenosine triphosphate; AMP, adenosine monophosphate.
Table 1List of Patients with Reported PTH Mutations and Their Genetic Features
Index case (sex, age) |
PTH mutation |
Homozygous, heterozygous, or other |
Familial |
Reference |
Male, infant |
c.52T>C p.C18R |
Heterozygous |
Yes |
[13] |
Female |
c.86+1G>C exon 2 skipped |
Homozygous |
Yes |
[18] |
Female, 7 days old |
c.67T>C p.S23P |
Homozygous |
Yes |
[19] |
Female, 59 years old |
c.247C>T p.R83X |
Somatic; hemizygous |
No |
[20] |
Female, 4 months old |
c.68C>A p.S23X |
Homozygous |
Yes |
[22] |
Female, 18 years old |
c.2T>C p.M1_D6del |
Heterozygous |
No |
[24] |
Male, early adolescence |
c.166C>T p.R56C |
Homozygous |
Yes |
[25] |
Male, 2 years old |
c.41T>A p.M14K |
Heterozygous |
Yes |
[27] |