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Skewed X inactivation in an X linked nystagmus family resulted from a novel, p.R229G, missense mutation in the FRMD7 gene
  1. Y Kaplan1,
  2. I Vargel2,
  3. T Kansu3,
  4. B Akin4,
  5. E Rohmann5,6,
  6. S Kamaci7,
  7. E Uz8,
  8. T Ozcelik8,
  9. B Wollnik5,6,
  10. N A Akarsu4,9
  1. 1
    Department of Neurology, Gaziosmanpaşa University, Medical Faculty, Tokat, Turkey
  2. 2
    Department of Plastic and Reconstructive Surgery, Hacettepe University Medical Faculty, Ankara, Turkey
  3. 3
    Department of Neurology, Hacettepe University Medical Faculty, Ankara, Turkey
  4. 4
    Gene Mapping Laboratory, Pediatric Hematology Unit, Hacettepe University Medical Faculty, Ankara, Turkey
  5. 5
    Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany
  6. 6
    Institute of Human Genetics, University of Cologne, Cologne, Germany
  7. 7
    Department of Orthodontics, Hacettepe University, Faculty of Dentistry, Ankara, Turkey
  8. 8
    Department of Molecular Biology and Genetics, Bilkent University, Faculty of Science, Ankara, Turkey
  9. 9
    Department of Medical Genetics, Hacettepe University Medical Faculty, Ankara, Turkey
  1. N A Akarsu, Hacettepe University Medical Faculty, Department of Pediatrics, Pediatric Hematology Unit, Gene Mapping Laboratory, Room No. 24, Sihhiye, 06100, Ankara, Turkey; nakarsu{at}


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.

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  • Funding: This study was supported by The Hacettepe University Research Foundation (number 00-01-101-010), The Scientific and Technological Research Council of Turkey (number TUBITAK-SBAG 3334) and The International Centre for Genetic Engineering and Biotechnology (ICGEB-CRP/TUR04-01).

  • Competing interests: None.