title: Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia-anophthalmia-coloboma (MAC) spectrum cases.
abstract: OBJECTIVE
  Microphthalmia-anophthalmia-coloboma (MAC) are congenital eye malformations causing a significant percentage of visually impairments in children. Although these anomalies can arise from prenatal exposure to teratogens, mutations in well-defined genes originate potentially heritable forms of MAC. Mutations in genes such as CHX10, GDF6, RAX, SOX2 and OTX2, among others, have been recognised in dominant or recessive MAC. SOX2 and OTX2 are the two most commonly mutated genes in monogenic MAC. However, as more numerous samples of MAC subjects would be analysed, a better estimation of the actual involvement of specific MAC-genes could be made. Here, a comprehensive mutational analysis of the CHX10, GDF6, RAX, SOX2 and OTX2 genes was performed in 50 MAC subjects.
  
  
  METHODS
  PCR amplification and direct automated DNA sequencing of all five genes in 50 unrelated subjects.
  
  
  RESULTS
  Eight mutations (16% prevalence) were recognised, including four GDF6 mutations (one novel), two novel RAX mutations, one novel OTX2 mutation and one SOX2 mutation. Anophthalmia and nanophthalmia, not previously associated with GDF6 mutations, were observed in two subjects carrying defects in this gene, expanding the spectrum of GDF6-linked ocular anomalies.
  
  
  CONCLUSIONS
  Our study underscores the importance of genotyping large groups of patients from distinct ethnic origins for improving the estimation of the global involvement of particular MAC-causing genes.
authors.affiliation: Research Unit, Institute of Ophthalmology Conde de Valenciana, Chimalpopoca 14, Col. Obrera, CP 06800, Mexico City, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Gonzalez-Rodriguez
authors.forename: E L
authors.initials: EL
authors.lastname: Pelcastre
authors.forename: J L
authors.initials: JL
authors.lastname: Tovilla-Canales
authors.forename: J E
authors.initials: JE
authors.lastname: Garcia-Ortiz
authors.forename: M
authors.initials: M
authors.lastname: Amato-Almanza
authors.forename: C
authors.initials: C
authors.lastname: Villanueva-Mendoza
authors.forename: Z
authors.initials: Z
authors.lastname: Espinosa-Mattar
authors.forename: J C
authors.initials: JC
authors.lastname: Zenteno
mesh_terms: D000853:Anophthalmos / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003103:Coloboma / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D005124:Eye Abnormalities / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D055431:Growth Differentiation Factor 6 / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D008800:Mexico; D008850:Microphthalmos / Q000235:genetics; D008875:Middle Aged; D051857:Otx Transcription Factors / Q000235:genetics; D017354:Point Mutation; D055748:SOXB1 Transcription Factors / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
chemical_list: D005136:Eye Proteins; C525906:GDF6 protein, human; D055431:Growth Differentiation Factor 6; D018398:Homeodomain Proteins; C497659:OTX2 protein, human; D051857:Otx Transcription Factors; C486393:RAX protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors; C490289:VSX2 protein, human