title: A novel mutation in FRMD7 causing X-linked idiopathic congenital nystagmus in a large family.
abstract: OBJECTIVE
  To identify the gene responsible for causing an X-linked idiopathic congenital nystagmus (XLICN) in a six-generation Chinese family.
  
  
  METHODS
  Forty-nine members of an XLICN family were recruited and examined after obtaining informed consent. Affected male individuals were genotyped with microsatellite markers around the FRMD7 locus. Mutations were comprehensively screened by direct sequencing using gene specific primers. An X-inactivation pattern was investigated by X chromosome methylation analysis.
  
  
  RESULTS
  The patients showed phenotypes consistent with XLICN. Genotype analysis showed that male affected individuals in the family shared a common haplotype with the selected markers. Sequencing FRMD7 revealed a G>T transversion (c.812G>T) in exon 9, which caused a conservative substitution of Cys to Phe at codon 271 (p.C271F). This mutation co-segregated with all affected individuals and was present in the obligate, non-penetrant female carriers. However, the mutation was not observed in unaffected familial males or 400 control males. Females with the mutant gene could be affected or carrier and they shared the same inactivated X chromosome harboring the mutation in blood cells, which showed there is no clear causal link between X-inactivation pattern and phenotype.
  
  
  CONCLUSIONS
  We identified a novel mutation in FRMD7 and confirmed the role of this mutation in the pathogenesis of X-linked congenital nystagmus.
authors.affiliation: Department of Genetics, National Research Institute for Family Planning, Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: He
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Yujing
authors.initials: Y
authors.lastname: Wang
authors.forename: Jinting
authors.initials: J
authors.lastname: Yan
authors.forename: Meng
authors.initials: M
authors.lastname: Zhang
authors.forename: Shangzhi
authors.initials: S
authors.lastname: Huang
authors.forename: Xu
authors.initials: X
authors.lastname: Ma
mesh_terms: D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002648:Child; D041321:Chromosomes, Human, X / Q000235:genetics; D003545:Cysteine; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006147:Guanine; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D020417:Nystagmus, Congenital / Q000235:genetics*; D010375:Pedigree; D010649:Phenylalanine; D013941:Thymine
chemical_list: D003598:Cytoskeletal Proteins; C516168:FRMD7 protein, human; D008565:Membrane Proteins; D010649:Phenylalanine; D006147:Guanine; D003545:Cysteine; D013941:Thymine