title: Allelic variation of the FRMD7 gene in congenital idiopathic nystagmus.
abstract: OBJECTIVE
  To perform a genotype-phenotype correlation study in an X-linked congenital idiopathic nystagmus pedigree (pedigree 1) and to assess the allelic variance of the FRMD7 gene in congenital idiopathic nystagmus.
  
  
  METHODS
  Subjects from pedigree 1 underwent detailed clinical examination including nystagmology. Screening of FRMD7 was undertaken in pedigree 1 and in 37 other congenital idiopathic nystagmus probands and controls. Direct sequencing confirmed sequence changes. X-inactivation studies were performed in pedigree 1.
  
  
  RESULTS
  The nystagmus phenotype was extremely variable in pedigree 1. We identified 2 FRMD7 mutations. However, 80% of X-linked families and 96% of simplex cases showed no mutations. X-inactivation studies demonstrated no clear causal link between skewing and variable penetrance.
  
  
  CONCLUSIONS
  We confirm profound phenotypic variation in X-linked congenital idiopathic nystagmus pedigrees. We demonstrate that other congenital nystagmus genes exist besides FRMD7. We show that the role of X inactivation in variable penetrance is unclear in congenital idiopathic nystagmus. Clinical Relevance We demonstrate that phenotypic variation of nystagmus occurs in families with FRMD7 mutations. While FRMD7 mutations may be found in some cases of X-linked congenital idiopathic nystagmus, the diagnostic yield is low. X-inactivation assays are unhelpful as a test for carrier status for this disease.
authors.affiliation: Clinical Neurosciences Division, University of Southampton, Southampton, England.
authors.forename: James E
authors.initials: JE
authors.lastname: Self
authors.forename: Fatima
authors.initials: F
authors.lastname: Shawkat
authors.forename: Crispin T
authors.initials: CT
authors.lastname: Malpas
authors.forename: N Simon
authors.initials: NS
authors.lastname: Thomas
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Harris
authors.forename: Peter R
authors.initials: PR
authors.lastname: Hodgkins
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Chen
authors.forename: Dorothy
authors.initials: D
authors.lastname: Trump
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lotery
mesh_terms: D000483:Alleles; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004584:Electronystagmography; D005133:Eye Movements; D005260:Female; D050172:Genes, X-Linked / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D020417:Nystagmus, Congenital / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D049951:X Chromosome Inactivation / Q000235:genetics
chemical_list: D003598:Cytoskeletal Proteins; C516168:FRMD7 protein, human; D008565:Membrane Proteins