Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene. Issue 1 (25th October 2007)

• Record Type: Journal Article
• Authors: Kaplan, Y; Vargel, I; Kansu, T; Akin, B; Rohmann, E; Kamaci, S; Uz, E; Ozcelik, T; Wollnik, B; Akarsu, N A
• Is Part Of: British journal of ophthalmology. Volume 92:Issue 1(2008)
• Page Start: 135
• Page End: 141
• Publication Date: 2007-10-25
• Subjects: Ophthalmology -- Periodicals; 617.7
• DOI: 10.1136/bjo.2007.128157
• Languages: English
• ISSNs: 0007-1161

Abstract

Abstract : 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.