Novel mutations in PAX6, OTX2 and NDP in anophthalmia, microphthalmia and coloboma

• DOI: 10.1038/ejhg.2015.155
• Publication Date: 2015-07-01T10:22:08Z
• Authors: Brett Deml; Linda M Reis; Emmanuelle Lemyre; Robin D Clark; Ariana Kariminejad; Elena V Semina
• Keywords: Anophthalmia; Proband; Coloboma

Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of eye. A/M is a highly heterogeneous disorder with SOX2 FOXE3 playing major roles dominant recessive pedigrees, respectively; however, majority cases lack genetic etiology. We analyzed 28 probands affected spectrum (without mutations SOX2/FOXE3) by whole-exome sequencing. Analysis 83 known factors identified pathogenic/likely pathogenic variants PAX6, OTX2 NDP three patients. A novel heterozygous likely variant c.767T>C, p.(Val256Ala), was two brothers bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea congenital glaucoma; unaffected mother appears to be mosaic carrier. While has been reported rare feature, this first report aphakia association PAX6 allele represents homeodomain associated A/M. OTX2, c.651delC, p.(Thr218Hisfs*76), patient syndromic anophthalmia hemizygous NDP, c.293 C>T, p.(Pro98Leu), isolated were also identified. Pathogenic/likely not discovered 25 remaining cases. This study underscores utility sequencing for identification causative variable phenotypes well extreme heterogeneity conditions.