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Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing compl

ObjectivesTo investigate retinal microstructure of patients affected with malattia leventinese (MLVT) and mutation in the EFEMP1 gene using high-resolution optical coherence tomography (OCT).MethodsPatients diagnosed with MLVT received a comprehensive eye exam, full-field and multifocal electroretinogram testing and imaging with a high-resolution Fourier domain OCT (Fd-OCT, UC Davis Medical Center, Davis, USA; axial resolution: 4.5 microm, acquisition speed: 9 frames s(-1), 1000 A scans s(-1)) combined with a flexible scanning head (Bioptigen Inc. Durham, NC, USA).ResultsTwo related patients aged 30 and 60 years, with MLVT and identified c.R345W mutation in the EFEMP1 gene, were tested. Mother and daughter showed a variable phenotype with reduced vision function in the younger patient, whereas the mother had a 'form frustre'. Fd-OCT revealed extensive or focal sub-retinal pigment epithelium (RPE) deposits, separation of RPE and Bruch's membrane, and disruption of the photoreceptor outer and inner segment layers. No outer retinal changes were visible outside areas with sub-RPE deposits.ConclusionRetinal structure in EFEMP1 retinal dystrophy is reflected by morphological changes within the RPE/Bruch's membrane complex with accumulation of sub-RPE material associated with disrupted photoreceptor integrity. The pattern of microstructural retinal abnormalities is similar but with a different extent in patients with variable phenotypes.

Ciliopathies, a growing pleotropic class of diseases due to mutations in genes that play an important role in primary cilia function. These highly conserved organelles are key to cell signaling. We now know, that mutations in one gene may lead to more than one ciliopathy phenotype and that one ciliopathy phenotype may be due to mutations in more than one gene. We studied the case of a female child with a novel ciliopathy phenotype and identified two novel mutations in the gene IFT80. Previously, mutations in IFT80 have been associated with a very narrow rib cage and failure of the lungs. Bone anomalies are also part of this IFT80‐condition but with no vision problems documented. Our case had none of the features known to be associated with IFT80 mutations and had retinal degeneration (RD). This work broadens the IFT80‐phenotype spectrum and also shows RD can be a feature of many ciliopathies. [ABSTRACT FROM AUTHOR]

PurposeTo describe the spectrum of phenotypic characteristics of BEST1-related autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a family with p.V86M mutation.MethodsA retrospective review of the clinical, psychophysical, and electrophysiological phenotypes of six subjects with ADVIRC. Five family members were sequenced for mutations in the BEST1gene.ResultsA heterozygous change, p.V86M (c.256G>A), was identified in the BEST1gene in the three affected subjects tested, and was shown to segregate with the disease phenotype. The distance visual acuity ranged from 20/25 to absent perception of light. Clinical features observed included angle closure glaucoma (n=2), microcornea with shallow anterior chamber (n=1), iris dysgenesis (n=2), cataracts (n=4), classical peripheral concentric band of retinal hyperpigmentation (n=5), and optic nerve dysplasia (n=1). Full-field electroretinogram response amplitudes ranged from low normal (two cases; 27 and 32 years) to non-recordable (two cases; 42 and 63 years). Goldmann fields were normal in two (27 and 28 years) but were abnormal in two older subjects. Optical coherence tomography showed macular thinning in the proband, whereas his affected daughter had normal macular thickness. Electro-oculography showed borderline Arden's ratio (1.50) in the lone case tested (27 years).ConclusionADVIRC is a slowly progressive vitreoretinal degeneration that demonstrates marked intra-familial phenotypic variability. Optic nerve dysplasia and iris dysgenesis are novel observations that extend the ocular phenotype of ADVIRC. [ABSTRACT FROM AUTHOR]

PurposeTo perform mutational screening of the visual system homeobox gene 1 (VSX1; MIM#605020) in patients with sporadic and familial keratoconus (MIM#148300) in a European population and, for the first time, report the mutational analysis of the two newly identified VSX1exons.MethodsVSX1sequence variants in patients with keratoconus were evaluated by direct sequencing of the entire coding region, including two novel exons. In familial keratoconus cases, segregation of potentially pathogenic VSX1variants was assessed to determine pathogenicity. Transcript analysis was carried out on splice site and synonymous sequence variants not detected in controls.ResultsA total of 66 unrelated patients with keratoconus from the European population (27 with familial keratoconus; 39 with sporadic keratoconus) were analysed for VSX1mutations. Four sequence variants were not observed in 100 healthy control individuals: c.432C>G (p.D144E), c.479G>A (p.G160D), c.789C>T (p.S263S), and an intronic change c.844-13T>A (numbered with respect to NM_014588). Segregation was not detected for p.D144E and c.844-13T>A. The change in p.G160D was observedin two patients with sporadic keratoconus. Although predicted to alter VSX1splicing, p.S263S had no effect on transcript processing. Four known SNPs were detected and the following polymorphic variants were observed in keratoconus patients and controls: c.711T>A (NM_199425; p.P237P), c.844-5_-6insT (NM_014588), c.*28G>T (DQ854811/DQ854812), and c.*50G>A (DQ854809/DQ854810).ConclusionsVSX1has a minor role in keratoconus pathogenesis. The pathogenicity of p.G160D remains controversial and this change may represent a rare polymorphism or genetic modifier. Further evidence is provided that the previously reported variant, p.D144E, is a polymorphism. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article on the characteristic of liver anomalies as a phenotype parameter of Bardet-Biedl syndrome.