KIF21A Mutations Research Articles

Congenital Fibrosis of Extraocular Muscles Type 1 with Progression of Ophthalmoplegia

Background 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. - Results We present a 60-year old patient with CFEOM1 due to the common C2860T mutation in KIF21A. At the age of 37, he complained about newly occurred diplopia, which implies the capability of binocular vision before. The divergence of both globes progressed and the poor residual movement on attempted adduction and upgaze completely disappeared during the sixths decade. Clinical and electromyographic examination showed isolated involvement of the oculomotor nerve. - Conclusion Apparently, progression of impaired ocular motility is not contradictory to the diagnosis of this congenital developmental disorder. Mechanical, contracture-like mechanisms as known from other types of strabism or persistent overuse of the reduced number of oculomotor a-motoneurons are generally considered as a reason for clinical progression. However, regarding the underlying known molecular basis of CFEOM1, a continuous disease progression due to the kinesin dysfunction cannot be excluded.

Identification of KIF21A mutations as a rare cause of congenital fibrosis of the extraocular muscles type 3 (CFEOM3).

Three congenital fibrosis of the extraocular muscles phenotypes (CFEOM1-3) have been identified. Each represents a specific form of paralytic strabismus characterized by congenital restrictive ophthalmoplegia, often with accompanying ptosis. It has been demonstrated that CFEOM1 results from mutations in KIF21A and CFEOM2 from mutations in PHOX2A. This study was conducted to determine the incidence of KIF21A and PHOX2A mutations among individuals with the third CFEOM phenotype, CFEOM3. All pedigrees and sporadic individuals with CFEOM3 in the authors' database were identified, whether the pedigrees were linked or consistent with linkage to the FEOM1, FEOM2, and/or FEOM3 loci was determined, and the appropriate pedigrees and the sporadic individuals were screened for mutations in KIF21A and PHOX2A. Twelve CFEOM3 pedigrees and 10 CFEOM3 sporadic individuals were identified in the database. The structures of eight of the pedigrees permitted the generation of meaningful linkage data. KIF21A was screened in 17 probands, and mutations were identified in two CFEOM3 pedigrees. One pedigree harbored a novel mutation (2841G-->A, M947I) and one harbored the most common and recurrent of the CFEOM1 mutations identified previously (2860C-->T, R954W). None of CFEOM3 pedigrees or sporadic individuals harbored mutations in PHOX2A. The results demonstrate that KIF21A mutations are a rare cause of CFEOM3 and that KIF21A mutations can be nonpenetrant. Although KIF21A is the first gene to be associated with CFEOM3, the results imply that mutations in the unidentified FEOM3 gene are the more common cause of this phenotype.

Mutations in KIF21A are responsible for CFEOM1 worldwide

Mutations in KIF21A are responsible for CFEOM1 worldwide