PT - JOURNAL ARTICLE AU - Y Kaplan AU - I Vargel AU - T Kansu AU - B Akin AU - E Rohmann AU - S Kamaci AU - E Uz AU - T Ozcelik AU - B Wollnik AU - N A Akarsu TI - Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the <em>FRMD7</em> gene AID - 10.1136/bjo.2007.128157 DP - 2008 Jan 01 TA - British Journal of Ophthalmology PG - 135--141 VI - 92 IP - 1 4099 - http://bjo.bmj.com/content/92/1/135.short 4100 - http://bjo.bmj.com/content/92/1/135.full SO - Br J Ophthalmol2008 Jan 01; 92 AB - 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&gt;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.