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Published on: June 16, 2020
Disruption of the PTHLH regulatory landscape results in features consistent with hyperparathyroid disease
Ashish R Deshwar1,2, Malte Spielmann3, Lisa Vi4
1Division of Clinical and Metabolic Genetics and University of Toronto, Department of Paediatrics, The Hospital for Sick Children, Toronto, Ontario, Canada.
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.
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