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

^*Korrespondierende/r Autor/-in für diese Arbeit

Institut für Humangenetik

2 Zitate (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.

Originalsprache	Englisch
Zeitschrift	American Journal of Medical Genetics, Part A
Jahrgang	179
Ausgabenummer	4
Seiten (von - bis)	663-667
Seitenumfang	5
ISSN	1552-4825
DOIs	https://doi.org/10.1002/ajmg.a.61071
Publikationsstatus	Veröffentlicht - 04.2019

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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.

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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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JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

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

Abstract

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