Ocular coloboma

Gene: TENM3

Green List (high evidence)

Associated with phenotype in OMIM, and a probable gene for Colobomatous microphthalmia in G2P.

PMID: 22766609 (2012) - Two affected sibs from a consanguineous Saudi family, with nonsyndromic bilateral microphthalmia, iris and retinal coloboma, and microcornea. Normal cognitive development was noted in both sibs. A homozygous 1 bp insertion (c.2083dup, p.T695Nfs*5) in the TENM3 gene, causing a frameshift predicted to result in premature truncation of the resulting protein, segregated with the phenotype. No other pathogenic variant were identified in any of the known microphthalmia genes.

PMID: 27103084 (2016) - In a patient with bilateral colobomatous microphthalmia authors identified a segregating homozygous splice site variant (c.2968‐2A>T, p.Val990Cysfs*13) in the TENM3 gene. His development was delayed, and he entered a specialised institution at the age of eight because of his apparent ID.

PMID: 30513139 (2018) - In two sisters with ocular coloboma and microcornea, but without microphthalmia, WES revealed a homozygous TENM3 variant (c.1857T>A, p. Cys619*). Sanger sequencing confirmed the parents were heterozygous carriers. Patient cells were not available for functional study of the variant. The older child (5.5 years old) was said to have global developmental delay; while the younger child (4 years 3 months old) had mild motor delay and spoke only few words, but cognition was reported normal.

PMID: 29753094 (2019) - 9-year-old boy with right eye microphthalmia, sclerocornea of both eyes, anterior segment dysgenesis, and severe global developmental delay, associated with compound heterozygous variants ([c.4046C>G, p.Ala1349Gly] ; [c.7687C>T, p.Arg2563Trp]) in the TENM3 gene. The p.Ala1349Gly variant was found in a heterozygous state in the proband's unaffected father and brother; however, the p.Arg2563Trp variant was not present in either parent, suggesting mosaicism in the mother or a de novo occurrence in the proband.

Created: 24 Aug 2020, 10:57 a.m. | Last Modified: 24 Aug 2020, 10:57 a.m.

Panel Version: 1.36

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microphthalmia, syndromic 15, 615145; ?Microphthalmia, isolated, with coloboma 9, 615145

Publications

• 22766609
• 27103084
• 30513139
• 29753094

Red List (low evidence)

Only reported in two families. No info on G2P

Created: 16 Nov 2016, 4:45 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Microphthalmia, isolated, with coloboma 9, 615145

Publications

• 22766609, 27103084, 24859618