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Current Osteoporosis Reports
Published in: Current Osteoporosis Reports 4/2016

01-08-2016 | Rare Bone Disease (CB Langman and E Shore, Section Editors)

Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations

Authors: Ernesto Canalis, Stefano Zanotti

Published in: Current Osteoporosis Reports | Issue 4/2016

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Abstract

Notch plays an important function in skeletal homeostasis, osteoblastogenesis, and osteoclastogenesis. Hajdu-Cheney syndrome (HCS) is a rare disease associated with mutations in NOTCH2 leading to the translation of a truncated NOTCH2 stable protein. As a consequence, a gain-of-NOTCH2 function is manifested. HCS is inherited as an autosomal dominant disease although sporadic cases exist. HCS is characterized by craniofacial developmental defects, including platybasia and wormian bones, osteoporosis with fractures, and acro-osteolysis. Subjects may suffer severe neurological complications, and HCS presents with cardiovascular defects and polycystic kidneys. An experimental mouse model harboring a HCSNotch2 mutation exhibits osteopenia secondary to enhanced bone resorption suggesting this as a possible mechanism for the skeletal disease. If the same mechanisms were operational in humans, anti-resorptive therapy could correct the bone loss, but not necessarily the acro-osteolysis. In conclusion, HCS is a devastating disease associated with a gain-of-NOTCH2 function resulting in diverse clinical manifestations.
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Metadata
Title
Hajdu-Cheney Syndrome, a Disease Associated with NOTCH2 Mutations
Authors
Ernesto Canalis
Stefano Zanotti
Publication date
01-08-2016
Publisher
Springer US
Published in
Current Osteoporosis Reports / Issue 4/2016
Print ISSN: 1544-1873
Electronic ISSN: 1544-2241
DOI
https://doi.org/10.1007/s11914-016-0311-6

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