TY - JOUR
T1 - Disruption of the PTHLH regulatory landscape results in features consistent with hyperparathyroid disease
AU - Deshwar, Ashish R.
AU - Spielmann, Malte
AU - Vi, Lisa
AU - Mendoza-Londono, Roberto
AU - Dupuis, Lucie
AU - Stimec, Jennifer
AU - Howard, Andrew
AU - Harrington, Jennifer
AU - Kannu, Peter
N1 - Funding Information:
We would like to thank the patient and their family for agreeing to participate in this case report. The content is solely the responsibility of the authors and does not necessarily represent the official views of the Mclaughlin Center.
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062326005&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.61071
DO - 10.1002/ajmg.a.61071
M3 - Journal articles
C2 - 30803154
AN - SCOPUS:85062326005
SN - 1552-4825
VL - 179
SP - 663
EP - 667
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 4
ER -
