title: Mutation analysis of KIF21A in congenital fibrosis of the extraocular muscles (CFEOM) patients.
abstract: OBJECTIVE
  CFEOM type 1 refers to a group of congenital eye movement disorders that is characterized by nonprogressive ophthalmoplegia affecting all the extraocular muscles. Individuals with the classic form of CFEOM are born with bilateral ptosis, infraducted eyes, and impossibility to raise their eyes above midline. This phenotype is often inherited as an autosomal dominant trait. CFEOM1 maps to the FEOM1 locus on chromosome 12 and is the consequence of mutations in the KIF21A gene. We analyzed three families and one sporadic case for potential genetic heterogeneity.
  
  
  METHODS
  Blood samples were collected from members of three families (Swiss, Turkish, and French origin) and one sporadic case (Iranian origin). In families, haplotype was tested for linkage to the autosomal dominant CFEOM1 locus on chromosome 12. Linkage studies were conducted using 2 polymorphic DNA microsatellite markers, D12S331 and D12S1048. Mutation analysis was performed by PCR amplification and bidirectional direct sequencing.
  
  
  RESULTS
  Haplotype analysis was compatible with linkage to the CFEOM1 locus in all affected members. Mutation analysis revealed the classical mutation R954W in all affected cases, including the sporadic case, regardless of their ethnic origin. The c.2860C>T base change was not observed in 100 individuals from various ethnic origins.
  
  
  CONCLUSIONS
  As reported, the classical c.2860C>T mutation represents a hotspot for mutation in various ethnic groups, including Swiss, Turkish, French, and Iranian patients. Sporadic cases are often due to neo-mutations as in our case. Mutation analysis is important, especially in sporadic cases, to correctly evaluate recurrence and transmission risks.
authors.affiliation: IRO-Institut de Recherche en Ophtalmologie, Sion, Switzerland. leila.tiab@iro.vsnet.ch
authors.forename: Leila
authors.initials: L
authors.lastname: Tiab
authors.forename: Violaine
authors.initials: V
authors.lastname: d'Allèves Manzi
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Borruat
authors.forename: Francis
authors.initials: F
authors.lastname: Munier
authors.forename: Daniel
authors.initials: D
authors.lastname: Schorderet
mesh_terms: D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D004252:DNA Mutational Analysis; D005152:Facial Muscles / Q000294:innervation* / Q000473:pathology; D005260:Female; D005355:Fibrosis; D008040:Genetic Linkage / Q000235:genetics*; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009801:Oculomotor Muscles / Q000294:innervation* / Q000473:pathology; D009886:Ophthalmoplegia / Q000151:congenital / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: C119023:KIF21A protein, human; D009419:Nerve Tissue Proteins; D016547:Kinesins