Endocrinol Metab.  2020 Mar;35(1):64-70. 10.3803/EnM.2020.35.1.64.

Rare PTH Gene Mutations Causing Parathyroid Disorders: A Review

  • 1Laboratory of Genomics and Translational Medicine, Gachon University College of Medicine, Incheon, Korea. shleemd@gachon.ac.kr
  • 2Department of Surgery, Gachon University College of Medicine, Incheon, Korea.
  • 3Department of Internal Medicine, Gachon University College of Medicine, Incheon, Korea.


Since parathyroid hormone (PTH) was first isolated and its gene (PTH) was sequenced, only eight PTH mutations have been discovered. The C18R mutation in PTH, discovered in 1990, was the first to be reported. This autosomal dominant mutation induces endoplasmic reticulum stress and subsequent apoptosis in parathyroid cells. The next mutation, which was reported in 1992, is associated with exon skipping. The substitution of G with C in the first nucleotide of the second intron results in the exclusion of the second exon; since this exon includes the initiation codon, translation initiation is prevented. An S23P mutation and an S23X mutation at the same residue were reported in 1999 and 2012, respectively. Both mutations resulted in hypoparathyroidism. In 2008, a somatic R83X mutation was detected in a parathyroid adenoma tissue sample collected from a patient with hyperparathyroidism. In 2013, a heterozygous p.Met1_Asp6del mutation was incidentally discovered in a case-control study. Two years later, the R56C mutation was reported; this is the only reported hypoparathyroidism-causing mutation in the mature bioactive part of PTH. In 2017, another heterozygous mutation, M14K, was detected. The discovery of these eight mutations in the PTH gene has provided insights into its function and broadened our understanding of the molecular mechanisms underlying mutation progression. Further attempts to detect other such mutations will help elucidate the functions of PTH in a more sophisticated manner.


Parathyroid glands; Genes; Mutation; Parathyroid hormone; Hypoparathyroidism; Hyperparathyroidism

MeSH Terms

Case-Control Studies
Codon, Initiator
Endoplasmic Reticulum Stress
Parathyroid Diseases*
Parathyroid Glands
Parathyroid Hormone
Parathyroid Neoplasms
Codon, Initiator
Parathyroid Hormone
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