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Mutational screening of CHX10, GDF6, OTX2, RAX and SOX2 genes in 50 unrelated microphthalmia–anophthalmia–coloboma (MAC) spectrum cases
  1. J Gonzalez-Rodriguez1,
  2. E L Pelcastre1,
  3. J L Tovilla-Canales2,
  4. J E Garcia-Ortiz3,
  5. M Amato-Almanza1,
  6. C Villanueva-Mendoza4,
  7. Z Espinosa-Mattar1,
  8. J C Zenteno1,5
  1. 1Research Unit, Institute of Ophthalmology “Conde de Valenciana” Mexico City, Mexico
  2. 2Department of Oculoplastics, Institute of Ophthalmology “Conde de Valenciana” Mexico City, Mexico
  3. 3Division of Genetics, Western Biomedical Research Center, Mexican Institute on Social Security, Guadalajara, Mexico
  4. 4Department of Genetics, Hospital “Dr. Luis Sanchez Bulnes”, Asociación Para Evitar la Ceguera en México, Mexico City, Mexico
  5. 5Department of Biochemistry, Faculty of Medicine, National Autonomous University of Mexico (UNAM), Mexico City, Mexico
  1. Correspondence to Dr Juan Carlos Zenteno, Department of Genetics, Institute of Ophthalmology “Conde de Valenciana”, Chimalpopoca 14, Col. Obrera, CP 06800, Mexico City, Mexico; jczenteno{at}


Background/aims 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.

Conclusion 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.

  • Anophthalmia
  • microphthalmia
  • eye coloboma
  • GDF6
  • RX
  • OTX2
  • SOX2
  • CHX10
  • Vision
  • Eye (Globe)
  • Genetics

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  • Competing interest None.

  • Ethics approval The study was approved by the Internal Review Board of the Institute of Ophthalmology ‘Conde de Valenciana’, at Mexico City.

  • Provenance and peer review Not commissioned; externally peer reviewed.