Affordable Access

deepdyve-link
Publisher Website

Exome sequencing identifies PDE4D mutations in acrodysostosis.

Authors
Type
Published Article
Journal
The American Journal of Human Genetics
Publisher
Elsevier
Volume
90
Issue
4
Pages
746–751
Identifiers
DOI: 10.1016/j.ajhg.2012.03.004
Source
Nelson Lab
License
Unknown

Abstract

Acrodysostosis is a dominantly-inherited, multisystem disorder characterized by skeletal, endocrine, and neurological abnormalities. To identify the molecular basis of acrodysostosis, we performed exome sequencing on five genetically independent cases. Three different missense mutations in PDE4D, which encodes cyclic AMP (cAMP)-specific phosphodiesterase 4D, were found to be heterozygous in three of the cases. Two of the mutations were demonstrated to have occurred de novo, providing strong genetic evidence of causation. Two additional cases were heterozygous for de novo missense mutations in PRKAR1A, which encodes the cAMP-dependent regulatory subunit of protein kinase A and which has been recently reported to be the cause of a form of acrodysostosis resistant to multiple hormones. These findings demonstrate that acrodysostosis is genetically heterogeneous and underscore the exquisite sensitivity of many tissues to alterations in cAMP homeostasis.

Report this publication

Statistics

Seen <100 times