Novel mutations in MYO7A and USH2A in Usher syndrome.

Purpose: Usher syndrome is an autosomal recessive disease associating retinitis pigmentosa and neurosensory deafness. Three clinical types (USH1, USH2, USH3) and 11 mutated genes or loci have been described. Mutations in MYO7A and USH2A are responsible for about 40% and 60% of Usher syndromes type 1 and 2, respectively.

Gene structure, chromosomal localization, and mutation screening of the human gene for the inner ear protein otospiralin.

Otospiralin is a novel protein of unknown function that is produced by non-sensory cells (fibrocytes) of the inner ear (cochlea and vestibule). We showed that downregulation of otospiralin in guinea pigs leads to deafness and we therefore hypothesized that genetic defects in the otospiralin gene could also cause deafness in humans. In this study, we cloned and localized OTOSP, the human gene for otospiralin.

Mutation spectrum and splicing variants in the OPA1 gene.

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy that features low visual acuity leading in many cases to legal blindness. We have recently shown, with others, that mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein, underlie the dominant form of optic atrophy. Here we report that OPA1 has eight mRNA isoforms as a result of the alternative splicing of exon 4 and two novel exons named 4b and 5b.

Retinal dystrophies caused by mutations in RPE65: assessment of visual functions.

Aims: To characterise the disease in patients with mutations in RPE65.

Methods: Individuals from two families were studied clinically.

Results: 13 and 20 year old compound heterozygote individuals from one family with R234X and 1121delA mutations showed nystagmus, macular dystrophy and low contrasted spots in the fundus.

[Molecular genetics of pigmentary retinopathies: identification of mutations in CHM, RDS, RHO, RPE65, USH2A and XLRS1 genes].

Purpose: To evaluate the occurrence and inheritance of various types of pigmentary retinopathy in patients followed at the outpatient clinic in the university hospital, Montpellier, France. To characterize genes and mutations causing these conditions.

Methods: Ophthalmic examination and various visual tests were performed.

Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy.

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic neuropathy occurring in 1 in 50,000 individuals that features progressive loss in visual acuity leading, in many cases, to legal blindness. Phenotypic variations and loss of retinal ganglion cells, as found in Leber hereditary optic neuropathy (LHON), have suggested possible mitochondrial impairment. The OPA1 gene has been localized to 3q28-q29 (refs 13-19).

Autosomal recessive retinal dystrophy associated with two novel mutations in the RPE65 gene.

Retinal dystrophies are a complex set of hereditary diseases of the retina that result in the degeneration of photoreceptors. Recent studies have shown that mutations in RPE65, a gene that codes for a retinal pigment epithelium (RPE)-specific protein thought to be involved in the 11-cis-retinoid metabolism, a key process in vision, cause severe, early onset retinal dystrophy. We describe two novel missense RPE65 mutations, L22P and H68Y, in a compound heterozygote with autosomal recessive retinal dystrophy.