Mutation in the human homeobox gene NKX5-3 causes an oculo-auricular syndrome

Am J Hum Genet. 2008 May;82(5):1178-84. doi: 10.1016/j.ajhg.2008.03.007.


Several dysmorphic syndromes affect the development of both the eye and the ear, but only a few are restricted to the eye and the external ear. We describe a developmental defect affecting the eye and the external ear in three members of a consanguineous family. This syndrome is characterized by ophthalmic anomalies (microcornea, microphthalmia, anterior-segment dysgenesis, cataract, coloboma of various parts of the eye, abnormalities of the retinal pigment epithelium, and rod-cone dystrophy) and a particular cleft ear lobule. Linkage analysis and mutation screening revealed in the first exon of the NKX5-3 gene a homozygous 26 nucleotide deletion, generating a truncating protein that lacked the complete homeodomain. Morpholino knockdown expression of the zebrafish nkx5-3 induced microphthalmia and disorganization of the developing retina, thus confirming that this gene represents an additional member implicated in axial patterning of the retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Consanguinity
  • Ear / abnormalities*
  • Embryo, Mammalian / metabolism
  • Embryo, Nonmammalian / metabolism
  • Eye Abnormalities / embryology
  • Eye Abnormalities / genetics*
  • Female
  • Fetus / metabolism
  • Homeodomain Proteins / biosynthesis
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Molecular Sequence Data
  • Organ Specificity
  • Pedigree
  • Syndrome
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Zebrafish / embryology
  • Zebrafish / metabolism


  • HMX1 protein, human
  • Homeodomain Proteins
  • Transcription Factors

Associated data

  • GENBANK/EU203551