Variants in the TUBB3 gene, one of the tubulin-encoding genes, are known to cause congenital fibrosis of the extraocular muscles type 3 and/or malformations of cortical development. Herein, we report a case of a 6-month-old infant with c.967A>G:p.(M323V) variant in the TUBB3 gene, who had only infantile nystagmus without other ophthalmological abnormalities. Subsequent brain magnetic resonance imaging (MRI) revealed cortical dysplasia. Neurological examinations did not reveal gross or fine motor delay, which are inconsistent with the clinical characteristics of patients with the M323V syndrome reported so far. A protein modeling showed that the M323V mutation in the TUBB3 gene interferes with αβ heterodimer formation with the TUBA1A gene. This report emphasizes the importance of considering TUBB3 and TUBA1A tubulinopathy in infantile nystagmus. A brain MRI should also be considered for these patients, although in the absence of other neurologic signs or symptoms.
Keywords: CFEOM3; TUBB3; congenital fibrosis of the extraocular muscle; infantile nystagmus; tubulinopathy.