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

Kaplan, Y.Vargel, I.Kansu, T.Akin, B.Rohmann, E.Kamaci, S.Uz, E.Ozcelik, T.Wollnik, B.Akarsu, N. A.2016-02-082016-02-0820080007-1161http://hdl.handle.net/11693/23235Aims: 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.EnglishAmino acidArginineGlycineCytoskeleton proteinFRMD7 protein, humanMembrane proteinUnclassified drugArticleCongenital nystagmusDNA methylationExonFamilyFemaleGene activationGene locusGene mutationGene sequenceGenetic linkageHeterozygosityHomozygosityHumanIntronMajor clinical studyMaleMissense mutationPhenotypePolymerase chain reactionPriority journalSubstitution reactionX chromosomeX chromosome linked disorderAdultAgedCongenital nystagmusEye diseaseGeneticsMethodologyMiddle agedNon insulin dependent diabetes mellitusNucleotide sequenceObesityPedigreeX chromosome inactivationX chromosome linked disorderBase SequenceCytoskeletal ProteinsDiabetes Mellitus, Type 2DNA Mutational AnalysisEye Diseases, HereditaryFemaleGenetic Diseases, X-LinkedHumansLinkage (Genetics)MaleMembrane ProteinsMiddle AgedMutation, MissenseNystagmus, CongenitalObesityPedigreeX Chromosome InactivationSkewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 geneArticle10.1136/bjo.2007.128157