Disruption of the PTHLH regulatory landscape results in features consistent with hyperparathyroid disease

Am J Med Genet A. 2019 Apr;179(4):663-667. doi: 10.1002/ajmg.a.61071. Epub 2019 Feb 25.

Abstract

Parathyroid hormone like hormone (PTHLH) signaling is essential for the proper formation of bone and its elevation or disruption has been directly implicated in several different skeletal dysplasias. We report a patient with a 2.802 Mb deletion upstream of the PTHLH coding sequence who presents with multiple fractures, metaphyseal changes, and overall features consistent with hyperparathyroid like disease. Analysis of the deleted region revealed the loss of putative regulatory regions adjacent to PTHLH and the possible gain of a limb enhancer. Furthermore, PTHLH expression appeared to be mis-regulated in fibroblasts derived from the patient. Altogether, we find that the disruption of the regulatory landscape of PTHLH likely results in its inappropriate expression and this novel clinical presentation.

Keywords: PTHLH; enhancer; hyperparathyroidism; parathyroid hormone like hormone.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Humans
  • Hyperparathyroidism / genetics*
  • Hyperparathyroidism / pathology*
  • Male
  • Mutation*
  • Parathyroid Hormone-Related Protein / genetics*
  • Prognosis
  • Regulatory Sequences, Nucleic Acid / genetics*

Substances

  • PTHLH protein, human
  • Parathyroid Hormone-Related Protein