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

Ashish R. Deshwar; Malte Spielmann; Lisa Vi; Roberto Mendoza-Londono; Lucie Dupuis; Jennifer Stimec; Andrew Howard; Jennifer Harrington; Peter Kannu

doi:10.1002/ajmg.a.61071

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

Ashish R. Deshwar, Malte Spielmann, Lisa Vi, Roberto Mendoza-Londono, Lucie Dupuis, Jennifer Stimec, Andrew Howard, Jennifer Harrington^*, Peter Kannu

^*Corresponding author for this work

Institute of Human Genetics

2 Citations (Scopus)

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.

Original language	English
Journal	American Journal of Medical Genetics, Part A
Volume	179
Issue number	4
Pages (from-to)	663-667
Number of pages	5
ISSN	1552-4825
DOIs	https://doi.org/10.1002/ajmg.a.61071
Publication status	Published - 04.2019

Funding

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 10 Reduced Inequalities

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10.1002/ajmg.a.61071

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title = "Disruption of the PTHLH regulatory landscape results in features consistent with hyperparathyroid disease",

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.",

author = "Deshwar, \{Ashish R.\} and Malte Spielmann and Lisa Vi and Roberto Mendoza-Londono and Lucie Dupuis and Jennifer Stimec and Andrew Howard and Jennifer Harrington and Peter Kannu",

note = "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: {\textcopyright} 2019 Wiley Periodicals, Inc. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",

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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 - https://www.scopus.com/pages/publications/85062326005

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JF - American Journal of Medical Genetics, Part A

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ER -

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

Abstract

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UN SDGs

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