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J. E. Self, F. Shawkat, C. Harris, S. Thomas, P. Hodgkins, X. Chen, A. Lotery; Assessment of the Allelic Variation of FRMD7 in X Linked Congenital Idiopathic Nystagmus. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1324.
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© ARVO (1962-2015); The Authors (2016-present)
To assess the allelic variation of FRMD7 in X linked congenital idiopathic nystagmus (CIN) and perform genotype-phenotype correlations in an extended X linked CIN pedigree.
A single pedigree with CIN inherited as an X-linked recessive trait underwent detailed clinical examination including infra-red limbal nystagmology and electrophysiological investigation in selected subjects. Following phenotyping and linkage analysis, screening of a recently identified nystagmus gene (FRMD7) was undertaken on our primary pedigree. 6 other X linked pedigrees, 3 possible x linked pedigrees and 28 simplex cases were also screened for FRMD7 mutations using a combination of SSCP and direct DNA sequencing. X inactivation studies were performed to investigate the hypothesised link between skewed X inactivation and variable penetrance in X linked CIN pedigrees.
We describe the results of detailed phenotyping including significant variability in clinical features between affected nystagmus patients with the same genetic mutation and illustrate the necessity of detailed eye movement recordings in family members to avoid diagnostic errors. We show how skewed X inactivation may contribute to the variable penetrance in females in CIN pedigrees. We also describe novel mutations in the FRMD7 gene and the prevalence of mutations in this gene in CIN pedigrees and simplex cases.
We show the necessity of accurate phenotyping in congenital nystagmus but that waveform analysis should be used with caution in the diagnostic setting. We have confirmed that FRMD7 mutations may cause nystagmus but that other significant nystagmus genes still exist. We also show that Skewing of X inactivation may indeed be responsible for the variable penetrance in females in X linked CIN families.
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