title: Fine mapping of the X-linked recessive congenital idiopathic nystagmus locus at Xq24-q26.3.
abstract: OBJECTIVE
  To refine the interval for X-linked congenital idiopathic nystagmus at Xq24-q26.3 and to evaluate a novel candidate gene (Muscleblind-like 3 gene [MBNL3]).
  
  
  METHODS
  A single pedigree with congenital idiopathic nystagmus (CIN) inherited as an X-linked recessive trait underwent detailed clinical examination including nystagmology and electrophysiological investigation in selected subjects. Following detailed phenotyping, genotyping was performed using 52 microsatellite markers spaced at an average of 5 cM along the X chromosome. Subsequent two-point and multipoint linkage analysis were performed and a candidate gene was screened for mutations by conventional sequencing.
  
  
  RESULTS
  Linkage mapping located the disease gene to a 15.5cM interval at Xq24-q26.3, between markers DXS1212 and DXS1062 with a maximum two-point LOD score of 4.24 with both markers DXS8044 and DXS994 (theta=0). Multipoint analysis indicated a LOD score of 4.54 and a critical gene interval of 8.0 cM. No mutations were found in the MBNL3 gene in this pedigree.
  
  
  CONCLUSIONS
  We describe a family with an unusual inheritance pattern most consistent with X-linked recessive inheritance with X inactivation causing manifesting females. We refine the linkage interval for X-linked recessive congenital idiopathic nystagmus and exclude MBNL3 as the causative gene in this family.
authors.affiliation: Clinical Neurosciences Division, University of Southampton, Southampton, UK.
authors.forename: James Edward
authors.initials: JE
authors.lastname: Self
authors.forename: Sarah
authors.initials: S
authors.lastname: Ennis
authors.forename: Andrew
authors.initials: A
authors.lastname: Collins
authors.forename: Fatima
authors.initials: F
authors.lastname: Shawkat
authors.forename: Christopher Mark
authors.initials: CM
authors.lastname: Harris
authors.forename: David Anthony
authors.initials: DA
authors.lastname: Mackey
authors.forename: Peter Robert
authors.initials: PR
authors.lastname: Hodgkins
authors.forename: Isabelle Karen
authors.initials: IK
authors.lastname: Temple
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Andrew John
authors.initials: AJ
authors.lastname: Lotery
mesh_terms: D002874:Chromosome Mapping; D041321:Chromosomes, Human, X; D004252:DNA Mutational Analysis; D005260:Female; D005808:Genes, Recessive; D050172:Genes, X-Linked; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D020417:Nystagmus, Congenital / Q000235:genetics*; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C467324:MBNL3 protein, human; D016601:RNA-Binding Proteins