Abstract:
Microphthalmia, anophthalmia, and coloboma (MAC) display a range of MAC ocular malformations. Anophthalmia (AO), and microphthalmia (MO), are the worst congenital deformities of the eye in terms of severity, with a prevalence of around 1 in 30,000 and 1 in 7,000 births, in turn. AO refers to the complete absence of the optic tissue structure or the structures of visible ocular with remnants that can be detected histologically. MO is defined as a decrease in the ocular globe size. Based on epidemiological studies, AO and MO have both heritable and environmental causes, with genetic defects being the majority of common causes. The proband described in this study was a 32-year-old symptomatic male with mild intellectual disability, bilateral decrease in the ocular globe size, and coloboma living in Sari city of Iran diagnosed as having non-syndromic bilateral colobomatous microphthalmia based on his clinical and paraclinical features. His parents were first cousins, and there was a positive family history in his pedigree. Human whole-exome enrichment was performed, and 35 genes related to the disease were analyzed. Sanger validation of theTENM3 gene endorsed the fact that the proband had a homozygous c.5069-1G>C variation. The detected homozygous canonical splice site variant in the TENM3 gene has not been reported up to now for its pathogenicity and can be considered as a novel mutation. Founded on the ACMG guideline, this variant can be categorized as pathogenic. The present finding can be used for genetic diagnosis and detection of carriers in the family and other patients with similar disease manifestations.