HOXA2 haploinsufficiency in dominant bilateral microtia and hearing loss

Kerry K. Brown, Lucas M. Viana, Cecilia C. Helwig, Maria A. Artunduaga, Lourdes Quintanilla-Dieck, Patricia Jarrin, Gabriel Osorno, Barbara Mcdonough, Steven R. Depalma, Roland D. Eavey, Jonathan G. Seidman, Christine E. Seidman

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1347-1351
Number of pages5
JournalHuman mutation
Issue number10
StatePublished - Oct 2013


  • Exome sequencing
  • HOXA2
  • Hearing loss
  • Microtia

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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