A total of 13 patients with genetically confirmed CFEOM (via genetic testing for mutations in KIF21A, PHOX2A, and TUBB3) were retrospectively identified after undergoing strabismus surgery at Boston Children's Hospital and surgical outcomes were compared.
A total of 13 patients with genetically confirmed CFEOM (via genetic testing for mutations in KIF21A, PHOX2A, and TUBB3) were retrospectively identified after undergoing strabismus surgery at Boston Children's Hospital and surgical outcomes were compared.
Point mutations in the KIF21A gene cause congenital fibrosis of the extraocular muscles type 1 (CFEOM1) by disrupting the autoinhibitory interaction between the motor domain and a regulatory region in the stalk.
Although mouse-model experiments have not revealed any findings of neuronal migration disorders, human TUBB3 mutations have been identified in patients with congenital fibrosis of the extraocular muscles.
Because TUBB3 mutations reported to cause CFEOM had not been associated with cortical malformations, while mutations reported to cause MCD had not been associated with CFEOM or other forms of paralytic strabismus, it was hypothesized that each set of mutations might alter microtubule function differently.
Maternal germline mosaicism of kinesin family member 21A (KIF21A) mutation causes complex phenotypes in a Chinese family with congenital fibrosis of the extraocular muscles.
Four unrelated participants, also not meeting MDC, had large-angle exotropia, vertical gaze deficiency, and ptosis consistent with congenital fibrosis of the extraocular muscles type 3 (CFEOM3); 1 patient harbored a novel TUBB3 mutation, and 3 patients harbored previously reported de novo TUBB3 mutations.
Mutations in KIF21A have been linked to congenital fibrosis of the extraocular muscles type 1 (CFEOM1), a dominant disorder associated with neurodevelopmental defects.
One of the eight TUBB3 mutations reported to cause congenital fibrosis of the extraocular muscles, c.1228G>A results in a TUBB3 E410K amino acid substitution that directly alters a kinesin motor protein binding site.
Kinesin family member 21A (KIF21A) mutation is the most common cause for congenital fibrosis of the extraocular muscles type 1 (CFEOM1) in populations worldwide.
CFEOM candidate gene analysis was performed in all patients and revealed a heterozygous p.R954WKIF21A mutation only in the patient who was not from a consanguineous family.
The purpose of this study was to determine if previously described Homo sapiens kinesin family member 21A (KIF21A) mutations were responsible for CFEOM in these two Chinese pedigrees.