Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene

Br J Ophthalmol. 2008 Jan;92(1):135-41. doi: 10.1136/bjo.2007.128157. Epub 2007 Oct 25.


Aims: This study aimed to identify the underlying genetic defect of a large Turkish X linked nystagmus (NYS) family.

Methods: Both Xp11 and Xq26 loci were tested by linkage analysis. The 12 exons and intron-exon junctions of the FRMD7 gene were screened by direct sequencing. X chromosome inactivation analysis was performed by enzymatic predigestion of DNA with a methylation-sensitive enzyme, followed by PCR of the polymorphic CAG repeat of the androgen receptor gene.

Results: The family contained 162 individuals, among whom 28 had NYS. Linkage analysis confirmed the Xq26 locus. A novel missense c.686C>G mutation, which causes the substitution of a conserved arginine at amino acid position 229 by glycine (p.R229G) in exon 8 of the FRMD7 gene, was observed. This change was not documented in 120 control individuals. The clinical findings in a female who was homozygous for the mutation were not different from those of affected heterozygous females. Skewed X inactivation was remarkable in the affected females of the family.

Conclusions: A novel p.R229G mutation in the FRMD7 gene causes the NYS phenotype, and skewed X inactivation influences the manifestation of the disease in X linked NYS females.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Base Sequence
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis / methods
  • Diabetes Mellitus, Type 2 / genetics
  • Eye Diseases, Hereditary / genetics*
  • Female
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Linkage
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation, Missense*
  • Nystagmus, Congenital / genetics*
  • Obesity / genetics
  • Pedigree
  • X Chromosome Inactivation


  • Cytoskeletal Proteins
  • FRMD7 protein, human
  • Membrane Proteins