KIF21A variant R954W in familial or sporadic cases of CFEOM1.
OBJECTIVE
To demonstrate the clinical characteristics and determine mutations in the KIF21A gene, encoding a kinesin motor protein in patients with congenital fibrosis of the extraocular muscles (CFEOM) type 1.


METHODS
Patients of five families with congenital fibrosis syndrome and two simplex patients with CFEOM underwent ophthalmologic examination and mutation analysis in the KIF21A gene.


RESULTS
Clinical examination and passive motility testing prior to surgery met criteria for CFEOM. All patients had congenital restrictive ophthalmoplegia primarily affecting muscles innervated by the oculomotor nerve. Complete mutation screening in the KIF21A gene revealed the presence of the known and most common recurrent variant R954W in three families and in two simplex cases. Two families demonstrated linkage to chromosome 16.


CONCLUSIONS
The patients included in the study had marked restriction of movement bilaterally with nearly complete loss of vertical ocular motility, graded reduction of horizontal motility, ptosis, and compensatory chin elevation. The phenotype was variable in patients carrying the same mutation. In one family, all patients were diagnosed with mental retardation, indicating that this syndrome might not only affect the development of cranial nerves, but can also be responsible for general neurologic dysfunction. The screening data suggest frequent and exclusive appearance of the R454W variant in sporadic and familial cases of CFEOM1 in Germany.
Rudolph
Guenther
G
Augenklinik der Ludwig-Maximilians-Universität, München - Germany. Guenther.Rudolph@med.uni-muechen.de
Nentwich
Michael
M
Hellebrand
Heide
H
Pollack
Katharina
K
Gordes
Roswitha
R
Bau
Viktoria
V
Kampik
Anselm
A
Meindl
Alfons
A
D000328:Adult; D001763:Blepharoptosis / Q000235:genetics*; D002675:Child, Preschool; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005355:Fibrosis / Q000151:congenital; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D009154:Mutation; D009801:Oculomotor Muscles / Q000473:pathology*; D017246:Ophthalmoplegia, Chronic Progressive External / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
C119023:KIF21A protein, human; D016547:Kinesins