These authors contributed equally to this work.
Identification of Novel Mutations Confirms PDE4D as a Major Gene Causing Acrodysostosis
Article first published online: 9 NOV 2012
© 2012 Wiley Periodicals, Inc.
Volume 34, Issue 1, pages 97–102, January 2013
How to Cite
Lynch, D. C., Dyment, D. A., Huang, L., Nikkel, S. M., Lacombe, D., Campeau, P. M., Lee, B., Bacino, C. A., Michaud, J. L., Bernier, F. P., Consortium, F. C., Parboosingh, J. S. and Innes, A. M. (2013), Identification of Novel Mutations Confirms PDE4D as a Major Gene Causing Acrodysostosis. Hum. Mutat., 34: 97–102. doi: 10.1002/humu.22222
This article was published online on 9 November 2012. Subsequently, it was determined that the gene and protein symbols were set incorrectly, and the corrected version was published online on 11 February 2013.
Contract Grant sponsors: Government of Canada through Genome Canada, the Canadian Institutes of Health Research; Ontario Genomics Institute (OGI-049); Genome Quebec; Genome British Columbia; CIHR Institute of Genetics Clinical Investigatorship Award (to D.A.D.); CIHR Training program in Genetics, Child Development and Health (to D.C.L).
Communicated by Arnold Munnich
- Issue published online: 20 DEC 2012
- Article first published online: 9 NOV 2012
- Accepted manuscript online: 3 OCT 2012 04:20AM EST
- Manuscript Accepted: 10 SEP 2012
- Manuscript Received: 16 APR 2012
- Government of Canada through Genome Canada
- the Canadian Institutes of Health Research
- Ontario Genomics Institute. Grant Number: OGI-049
- Genome Quebec; Genome British Columbia
- Institute of Genetics Clinical Investigatorship
Vol. 34, Issue 4, 667, Article first published online: 11 FEB 2013
Acrodysostosis is characterized by nasal hypoplasia, peripheral dysostosis, variable short stature, and intellectual impairment. Recently, mutations in PRKAR1A were reported in patients with acrodysostosis and hormone resistance. Subsequently, mutations in a phosphodiesterase gene (PDE4D) were identified in seven sporadic cases. We sequenced PDE4D in seven acrodysostosis patients from five families. Missense mutations were identified in all cases. Families showed de novo inheritance except one family with three affected children whose father was subsequently found to have subtle features of acrodysostosis. There were no recurrent mutations. Short stature and endocrine resistance are rare in this series; however, cognitive involvement and obesity were frequent. This last finding is relevant given PDE4D is insulin responsive and potentially involved in lipolysis. PDE4D encodes a cyclic AMP regulator and places PDE4D-related acrodysostosis within the same family of diseases as pseudohypoparathyroidism, pseudopseudohypoparathyroidism, PRKAR1A-related acrodysostosis and brachydactyly-mental retardation syndrome; all characterized by cognitive impairment and short distal extremities.