Congenital fibrosis of the extraocular muscles type 1 (CFEOM1) is a congenital, non-progressive autosomal-dominant disorder with bilateral oculomotor nerve palsy due to mutations in the kinesin motor protein gene KIF21A.-
To further define the spectrum of KIF21A mutations in CFEOM we have now identified all CFEOM probands newly enrolled in our study and determined if they harbor mutations in KIF21A.
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.
The disorder was tested for linkage to two known autosomal dominant CFEOM loci on chromosome 12p11.2-q12 (CFEOM1) and chromosome 16q24 (CFEOM3) using microsatellite markers.
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.
We report familial segregation of hereditary total leuconychia (HTL) with ptosis and restriction of ocular motility due to congenital fibrosis of the extraocular muscles type 1 (CFEOM1) in three generations.
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.
Linkage analysis with microsatellite markers at chromosome 12q and direct sequence analysis of the KIF21A gene were performed on three families and one sporadic CFEOM case.
A major mutation of KIF21A associated with congenital fibrosis of the extraocular muscles type 1 (CFEOM1) enhances translocation of Kank1 to the membrane.