SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia

Eur J Med Genet. 2015 Feb;58(2):66-70. doi: 10.1016/j.ejmg.2014.12.005. Epub 2014 Dec 23.

Abstract

Anophthalmia (A) and microphthalmia (M) are rare developmental anomalies that have significant effects on visual activity. In fraction of A/M subjects, single genetic defects have been identified as causative. In this study we analysed 65 Italian A/M patients, 21 of whom are syndromic, for mutations in SOX2, OTX2 and PAX6 genes. In syndromic patients the presence of genome imbalances through array CGH was also investigated. No mutations were found for OTX2 and PAX6 genes. Three causative SOX2 mutations were found in subjects with syndromic A. In a subject with syndromic signs and monolateral M, two de novo 6.26 Mb and 1.37 Mb deletions in 4q13.2q13.3 have been identified. A SOX2 missense (p.Ala161Ser) mutation was found in 1 out of 39 a subject with non-syndromic monolateral M. Alanine at position 161 is conserved along phylogeny and the p.Ala161Ser mutation is estimated pathogenic by in silico analysis. However, this mutation was also present in the unaffected patient's daughter.

Keywords: Anophthalmia; Microphthalmia; OTX2; PAX6; SOX2.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anophthalmos / genetics*
  • Child
  • Child, Preschool
  • Eye Proteins / genetics*
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Italy
  • Male
  • Microphthalmos / genetics*
  • Middle Aged
  • Mutation
  • Otx Transcription Factors / genetics*
  • PAX6 Transcription Factor
  • Paired Box Transcription Factors / genetics*
  • Repressor Proteins / genetics*
  • SOXB1 Transcription Factors / genetics*
  • Young Adult

Substances

  • Eye Proteins
  • Homeodomain Proteins
  • OTX2 protein, human
  • Otx Transcription Factors
  • PAX6 Transcription Factor
  • PAX6 protein, human
  • Paired Box Transcription Factors
  • Repressor Proteins
  • SOX2 protein, human
  • SOXB1 Transcription Factors