Re-use of this article is permitted in accordance with the Terms and Conditions set out at http://wileyonlinelibrary.com/onlineopen#OnlineOpen_Terms
Mutations in the NOG gene are commonly found in congenital stapes ankylosis with symphalangism, but not in otosclerosis
Article first published online: 30 JAN 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 82, Issue 6, pages 514–520, December 2012
How to Cite
Usami, S., Abe, S., Nishio, S., Sakurai, Y., Kojima, H., Tono, T. and Suzuki, N. (2012), Mutations in the NOG gene are commonly found in congenital stapes ankylosis with symphalangism, but not in otosclerosis. Clinical Genetics, 82: 514–520. doi: 10.1111/j.1399-0004.2011.01831.x
- Issue published online: 6 NOV 2012
- Article first published online: 30 JAN 2012
- Received 9 August 2011, revised and accepted for publication 12 December 2011
- stapes ankylosis;
- stapes ankylosis with broad;
- Teunissen and Cremer syndrome;
- thumb and toes
Usami S, Abe S, Nishio S, Sakurai Y, Kojima H, Tono T, Suzuki N. Mutations in the NOG gene are commonly found in congenital stapes ankylosis with symphalangism, but not in otosclerosis.
Human noggin (NOG) is a responsible gene for multiple synostosis syndrome (SYNS1) and proximal symphalangism (SYM1), two conditions that are recently known to be within a wider range of clinical manifestations of stapes ankylosis with symphalangism. This study was performed to determine the range of phenotype caused by NOG mutations, using Japanese patients with various phenotypes including sporadic inherited SYM1, dominantly inherited SYM1, stapes ankylosis with broad thumb and toes (Teunissen and Cremer syndrome). In addition, 33 patients with typical otosclerosis (without symphalangism) were studied. Direct sequencing analysis disclosed three novel mutations of the NOG gene in three SYM1 families. None of the otosclerosis patients without symphalangism had NOG mutations, indicating that NOG mutations may be restrictively found within patients with various skeletal abnormalities. These results together with the literature review indicated that there are no clear genotype–phenotype correlations for NOG mutations. With regard to surgical outcome, most of the patients in these three families with NOG mutations showed remarkable air–bone gap recovery after stapes surgery. Molecular genetic testing is useful to differentiate syndromic stapes ankylosis from otosclerosis, and even mild skeletal anomalies can be a diagnostic indicator of NOG-associated disease.