A new autosomal recessive syndrome consisting of posteriormicrophthalmos, retinitis pigmentosa, foveoschisis, and optic discdrusen is caused by a MFRP gene mutation

[摘要] Purpose: To describe the clinical and genetic characteristics of anew ophthalmic syndrome, which consists of posterior microphthalmos,retinitis pigmentosa, foveoschisis, and optic disc drusen, thatsegregates as an autosomal recessive trait in a family with fouraffected siblings. The membrane-type frizzled-related protein (MFRP)and CEH10 homeodomain-containing homolog (CHX10) genes, previouslyimplicated in autosomal recessive forms of nanophthalmos/microphthalmos,were analyzed as candidate genes for this novel disease.Methods: Complete ophthalmologic examinations were performed in fouraffected siblings and their parents. Ophthalmologic manifestations,fundus photographs, ultrasonographic (US) assessment,electroretinography (ERG), fluorescein retinal angiography (FA),Goldmann kinetic perimetry (GKP), and optical coherence tomography(OCT), as well as mutational status of MFRP and CHX10 genes ingenomic DNA.Results: In all affected siblings, ophthalmologic examinationdemonstrated normal horizontal corneal diameters and high hyperopia;funduscopy, ERG, and FA evidenced a progressive retinal dystrophycompatible with retinitis pigmentosa; A- and B-mode ultrasonographyrevealed decreased axial eye length and optic disc drusen; OCT showedlocalized macular retinoschisis. MFRP molecular analysis disclosed aone base pair insertion in exon 5 (c.498_499insC) in all affectedindividuals, a mutation that predicts a truncated protein (P165fsX198).Both parents were heterozygous for this mutation.Conclusions: A distinct autosomal recessive ophthalmic syndromecharacterized by microphthalmos, retinitis pigmentosa, foveoschisis, andoptic disc drusen is described. We demonstrated that this clinicalassociation is caused by a mutation in MFRP, a gene previouslyimplicated in isolated nanophthalmos. Our data indicate that defects inMFRP could be responsible for syndromic forms ofmicrophthalmos/retinal degeneration and that this gene is necessary forphotoreceptor maintenance.

[学科分类] 生物化学/生物物理