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H. Kondo, M. Qin, H. Hayashi, K. Oshima, T. Tahira, K. Hayashi; FZD4 and/or LRP5 Gene Mutations in 14 Japanese Families With Familial Exudative Vitreoretinopathy . Invest. Ophthalmol. Vis. Sci. 2005;46(13):1797.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To search for mutations in frizzled–4 (FZD4) and low–density–lipoprotein receptor–related protein 5 (LRP5) in patients with autosomal dominant familial exudative vitreoretinopathy (FEVR) and to delineate the defective–gene–associated clinical features. Methods: Direct sequencing following polymerase chain reaction of all coding exons of FZD4 and LRP5 was performed for 56 probands of 31 familial and 25 simplex FEVR, and some of their families. Clinical symptoms among patients with mutations were assessed. Results: Four mutations in FZD4 (M105V, W319X, R417Q and G488D) in five patients were reported previously (ARVO 2003 and Br J Ophthalmol 2003). Six novel mutations in either LRP5 (L145F, R444C, A522T, T798A and N1121D) or FZD4 (W335C) were identified in six familial cases. Four novel mutations in LRP5 (T535M, F617C, G268fsX272 and G610R) and one known mutation in FZD4 (M342V) were detected in three simplex cases; two of these patients carried compound heterozygous mutations in LRP5, indicative of autosomal recessive inheritance. Remarkably, R444C in LRP5 was found in the family in which R417Q in FZD4 had been identified. The severity of vitreoretinopathy in these patients varied, however, low bone mass was highly associated with patients haboring LRP5 mutations. Conclusions: Some of the FEVR patients may have a complex genetic trait not accounted for by simple monogenic inheritance, and presence or absence of low bone mass may have some implications for the distinct clinical phenotype found among FEVR–causing mutations, a point of consideration needed in clinical genetic diagnosis.
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