VAX1 mutation associated with microphthalmia, corpus callosum agenesis, and orofacial clefting: the first description of a VAX1 phenotype in humans

Hum Mutat. 2012 Feb;33(2):364-8. doi: 10.1002/humu.21658. Epub 2011 Dec 27.

Abstract

Vax1 and Vax2 have been implicated in eye development and the closure of the choroid fissure in mice and zebrafish. We sequenced the coding exons of VAX1 and VAX2 in 70 patients with anophthalmia/microphthalmia (A/M). In VAX1, we observed homozygosity for two successive nucleotide substitutions c.453G>A and c.454C>A, predicting p.Arg152Ser, in a proband of Egyptian origin with microphthalmia, small optic nerves, cleft lip/palate, and corpus callosum agenesis. This mutation affects an invariant residue in the homeodomain of VAX1 and was absent from 96 Egyptian controls. It is likely that the mutation results in a loss of function, as the mutation results in a phenotype similar to the Vax1 homozygous null mouse. We did not identify any mutations in VAX2. This is the first description of a phenotype associated with a VAX1 mutation in humans and establishes VAX1 as a new causative gene for A/M.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Agenesis of Corpus Callosum / genetics*
  • Amino Acid Substitution
  • Child, Preschool
  • Cleft Lip / genetics*
  • Cleft Palate / genetics*
  • Exons
  • Gene Frequency
  • HEK293 Cells
  • Homeodomain Proteins / genetics*
  • Homozygote
  • Humans
  • Male
  • Microphthalmos / genetics*
  • Mutation*
  • Phenotype*
  • Transcription Factors / genetics*

Substances

  • Homeodomain Proteins
  • Transcription Factors
  • VAX1 protein, human
  • VAX2 protein, human