RT Journal Article
SR Electronic
T1 Mutational screening of <em>CHX10, GDF6, OTX2, RAX</em> and <em>SOX2</em> genes in 50 unrelated microphthalmia–anophthalmia–coloboma (MAC) spectrum cases
JF British Journal of Ophthalmology
JO Br J Ophthalmol
FD BMJ Publishing Group Ltd.
SP 1100
OP 1104
DO 10.1136/bjo.2009.173500
VO 94
IS 8
A1 J Gonzalez-Rodriguez
A1 E L Pelcastre
A1 J L Tovilla-Canales
A1 J E Garcia-Ortiz
A1 M Amato-Almanza
A1 C Villanueva-Mendoza
A1 Z Espinosa-Mattar
A1 J C Zenteno
YR 2010
UL http://bjo.bmj.com/content/94/8/1100.abstract
AB 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.