Sequence variations in TENM3 gene causing eye anomalies with intellectual disability: Expanding the phenotypic spectrum

Abstract Microphthalmia, anophthalmia are the malformations of the eye, referring to a congenital absence, and a reduced size of the eyeball. Coloboma of iris is associated with many of the cases. Here, we report a propositus with eye anomalies and intellectual disability associated with TENM3 pathogenic variations identified by exome sequencing and confirms intellectual disability as a phenotype associated with TENM3 variations. This child was compound heterozygote [NM_001080477.3(TENM3):c.4046C > G; p.(Ala1349Gly) and NM_001080477.3( TENM3 ): c.7687C > T; p.(Arg2563Trp)] for the missense likely pathogenic sequence variations in TENM3 gene. To our knowledge only three patients till now have been reported to have TENM3 pathogenic variations in association with microphthalmia, two siblings without developmental delay and third with developmental delay. This report supports the association of TENM3 variations with colobomatous microphthalmia and expands the phenotypic spectrum associated with pathogenic variations in this gene.