Abstract

Anophthalmia or microphthalmia (A/M) is a rare group of congenital/developmental ocular malformations, characterized by absent or small eye within the orbit affecting one or both eyes. It has complex etiology with chromosomal, monogenic with high heterogeneity, and environmental causes. We performed genome SNP-array analysis followed by autozygosity mapping and sequencing in the members of two families in which three individuals are suffering from severe bilateral anophthalmia. The genetic analysis revealed a novel missense c.709G>A mutation in exon 7 of ALDH1A3 (aldehyde dehydrogenase 1 family member A3), causing a substitution of glycine (Gly) to arginine (Arg) at residue 237. This study consolidates the importance of ALDH1A3 gene screening in autosomal recessive anophthalmia. This variation may also be suggestive of a founder effect in the southeastern area of Iran.