title: KIF21A variant R954W in familial or sporadic cases of CFEOM1.
abstract: 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.
authors: Augenklinik der Ludwig-Maximilians-Universität, München - Germany. Guenther.Rudolph@med.uni-muechen.de
authors: Guenther
authors: G
authors: Rudolph
authors: Michael
authors: M
authors: Nentwich
authors: Heide
authors: H
authors: Hellebrand
authors: Katharina
authors: K
authors: Pollack
authors: Roswitha
authors: R
authors: Gordes
authors: Viktoria
authors: V
authors: Bau
authors: Anselm
authors: A
authors: Kampik
authors: Alfons
authors: A
authors: Meindl
mesh_terms: 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
chemical_list: C119023:KIF21A protein, human; D016547:Kinesins