These authors contributed equally to this work.
HOXA2 Haploinsufficiency in Dominant Bilateral Microtia and Hearing Loss
Article first published online: 11 JUL 2013
© 2013 WILEY PERIODICALS, INC.
Volume 34, Issue 10, pages 1347–1351, October 2013
How to Cite
Brown, K. K., Viana, L. M., Helwig, C. C., Artunduaga, M. A., Quintanilla-Dieck, L., Jarrin, P., Osorno, G., McDonough, B., DePalma, S. R., Eavey, R. D., Seidman, J. G. and Seidman, C. E. (2013), HOXA2 Haploinsufficiency in Dominant Bilateral Microtia and Hearing Loss. Hum. Mutat., 34: 1347–1351. doi: 10.1002/humu.22367
Grant sponsors: Howard Hughes Medical Institute; NHLBI.
Communicated by Nancy B. Spinner
- Issue published online: 18 SEP 2013
- Article first published online: 11 JUL 2013
- Accepted manuscript online: 17 JUN 2013 07:45AM EST
- Manuscript Accepted: 4 JUN 2013
- Manuscript Received: 29 MAR 2013
- Howard Hughes Medical Institute
- hearing loss;
- exome sequencing;
Microtia is a rare, congenital malformation of the external ear that in some cases has a genetic etiology. We ascertained a three-generation family with bilateral microtia and hearing loss segregating as an autosomal dominant trait. Exome sequencing of affected family members detected only seven shared, rare, heterozygous, nonsynonymous variants, including one protein truncating variant, a HOXA2 nonsense change (c.703C>T, p.Q235*). The HOXA2 variant was segregated with microtia and hearing loss in the family and was not seen in 6,500 individuals sequenced by the NHLBI Exome Sequencing Project or in 218 control individuals sequenced in this study. HOXA2 has been shown to be critical for outer and middle ear development through mouse models and has previously been associated with autosomal recessive bilateral microtia. Our data extend these conclusions and define HOXA2 haploinsufficiency as the first genetic cause for autosomal-dominant nonsyndromic microtia.