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Disruption of the PTHLH regulatory landscape results in features consistent with hyperparathyroid disease
Author(s) -
Deshwar Ashish R.,
Spielmann Malte,
Vi Lisa,
MendozaLondono Roberto,
Dupuis Lucie,
Stimec Jennifer,
Howard Andrew,
Harrington Jennifer,
Kannu Peter
Publication year - 2019
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.61071
Subject(s) - enhancer , regulatory sequence , parathyroid hormone , coding region , cancer research , biology , transcription factor , medicine , endocrinology , genetics , gene , calcium
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.