A Novel Mutation ConfirmsMFRPas the Gene Causing the Syndrome of Nanophthalmos-Renititis Pigmentosa-Foveoschisis-Optic Disk Drusen

• Published in: American journal of ophthalmology 2008-08, Vol.146 (2), p.323
• Main Authors: Crespí, Jaume, Buil, José A, Bassaganyas, Francisca, Vela-Segarra, José I, Díaz-Cascajosa, Jesús, Ayala-Ramírez, Raul, Zenteno, Juan C
• Format: Article
• Language: English
• Subjects: Amino acids; Deoxyribonucleic acid; DNA; Genotype & phenotype; Macular degeneration; Mutation; Patients; Proteins
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2008.04.029

Purpose To describe the clinical and genetic characteristics of the second family with a recently described recessive syndrome characterized by posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disk drusen. Design Observational case report. Methods Three affected subjects and one healthy sibling from a consanguineous marriage from Spain were studied. Complete ophthalmologic examinations including A- and B-mode ultrasonography (US), electroretinography (ERG), fluorescein retinal angiography (FA), and optical coherence tomography (OCT) were performed in each individual. Genetic analysis included polymerase chain reaction amplification and direct nucleotide sequencing of the completeMFRPgene. Results All three affected siblings had bilateral shortening of the posterior ocular segment associated with high hyperopia and normal anterior segment dimensions. Best-corrected visual acuity ranged from 20/200 to 20/60. Funduscopy, ERG, and FA were compatible with retinitis pigmentosa, and B-mode ultrasound showed optic disk drusen. OCT analysis revealed outer retinal layer schisis with absence of foveal pit. Inheritance of this syndrome followed an autosomal recessive pattern. Molecular analysis revealed a novel homozygous 1-bp deletion (c.498delC) in exon 5 ofMFRP, predicting a prematurely truncated protein (P166fsX190). A healthy sister demonstrated to be a carrier of the mutation. Conclusions We confirmed that the syndrome of posterior microphthalmos, retinitis pigmentosa, foveoschisis, and optic disk drusen constitutes a distinct autosomal recessive entity. The novel frameshift mutation identified in the family described here validatesMFRPas the gene responsible for this particular disease, which characteristically involves structures located at the posterior segment of the eye.