HOXA2 haploinsufficiency in dominant bilateral microtia and hearing loss.
Publication/Presentation Date
10-1-2013
Abstract
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.
Volume
34
Issue
10
First Page
1347
Last Page
1351
ISSN
1098-1004
Published In/Presented At
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., & Seidman, C. E. (2013). HOXA2 haploinsufficiency in dominant bilateral microtia and hearing loss. Human mutation, 34(10), 1347–1351. https://doi.org/10.1002/humu.22367
Disciplines
Medicine and Health Sciences
PubMedID
23775976
Department(s)
Department of Pathology and Laboratory Medicine
Document Type
Article