Aim: To characterise the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with the Arg844His mutation in RIM1. Methods: Eight members of a four generation, non-consanguineous British family wer...Aim: To characterise the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with the Arg844His mutation in RIM1. Methods: Eight members of a four generation, non-consanguineous British family were examined clinically and underwent electrophysiological testing, automated dark adapted perimetry, dark adaptometry, colour vision assessment, colour fundus photography, fundus fluorescein angiography (FFA), and fundus autofluorescence (AF) imaging. Results: The majority of affected individuals described a progressive deterioration of central vision, night vision, and peripheral visual field usually between the third and fourth decades. The visual acuity ranged from 6/6 to3/60. Colour vision testing showed mild to moderate dyschromatopsia in the majority of individuals. Fundus changes comprised a range of macular appearances varying from mild retinal pigment epithelial (RPE) disturbance to extensive atrophy and pigmentation. In some individuals retinal vessels were attenuated and in two subjects peripheral areas of retinal atrophy were present. An absent or severely reduced PERG was detected in all subjects, indicative of marked macular dysfunction. Full field ERG showed abnormal rod and cone responses. AF imaging revealed decreased macular AF centrally surrounded by a ring of increased AF in the majority of individuals. “ Bull’ s eye” lesions were present in two individuals, comprising of a ring of decreased perifoveal AF bordered peripherally and centrally by increased AF. Photopic sensitivity testing demonstrated elevated central visual field thresholds with additional superior greater than inferior peripheral field loss. There were rod and cone sensitivity reductions in the central and peripheral visual fields, with the inferior retina being more affected than the superior. Conclusions: The detailed phenotype is described of the autosomal dominant cone-red dystrophy, CORD7, which is associated with a point mutation in RIM1, a gene encoding a photoreceptor synaptic protein. The pattern of disease progression and long term visual outcome facilitates improved genetic counselling and advice on prognosis. Such phenotypic data will be invaluable in the event of future therapy.展开更多
Aims: To characterise the detailed phenotype of “cone dystrophy with supernor mal rod ERG”in a case series of 10 patients. Methods: 10 affected patients were examined clinically and underwent colour fundus photograp...Aims: To characterise the detailed phenotype of “cone dystrophy with supernor mal rod ERG”in a case series of 10 patients. Methods: 10 affected patients were examined clinically and underwent colour fundus photography, with nine undergoi ng detailed electrophysiological testing. Five patients were assessed further wi th fundus autofluorescence (AF)imaging, automated photopic and dark adapted peri metry, and dark adaptometry. Detailed colour vision assessment was performed in six subjects. Blood samples were taken from four patients for DNA extraction and mutation screening of NR2E3was undertaken. Results: The onset of symptoms was i n the first and second decades of life. Subjects presented with reduced central vision and marked photophobia. All individuals were myopic and colour vision tes ting revealed severely reduced colour discrimination predominantly along the red -green axes; tritan colour vision was relatively well preserved. Nyctalopia is a later feature of the disorder. Funduscopy and AF imaging revealed a range of m acular appearances. There was electrophysiological evidence of marked macular dy sfunction, reduced and delayed cone responses, and supernormal and delayed rod r esponses. Photopic and dark adapted perimetry revealed central scotomata with wi despread peripheral sensitivity loss. No disease causing sequence variants in NR 2E3 were identified. Conclusions: The largest case series to date has been descr ibed of the clinical, psychophysical and electrophysiological characteristics of this unusual cone dystrophy with supernormal rod responses. Electrophysiologica l data were consistent with a post-phototransduction, but pre-inner nuclear la yer, site of dysfunction. While the definitive diagnosis can only be made with e lectrophysiological testing, several characteristics that may increase suspicion of this diagnosis are presented.展开更多
文摘Aim: To characterise the phenotype of an autosomal dominant cone-rod dystrophy (CORD7) associated with the Arg844His mutation in RIM1. Methods: Eight members of a four generation, non-consanguineous British family were examined clinically and underwent electrophysiological testing, automated dark adapted perimetry, dark adaptometry, colour vision assessment, colour fundus photography, fundus fluorescein angiography (FFA), and fundus autofluorescence (AF) imaging. Results: The majority of affected individuals described a progressive deterioration of central vision, night vision, and peripheral visual field usually between the third and fourth decades. The visual acuity ranged from 6/6 to3/60. Colour vision testing showed mild to moderate dyschromatopsia in the majority of individuals. Fundus changes comprised a range of macular appearances varying from mild retinal pigment epithelial (RPE) disturbance to extensive atrophy and pigmentation. In some individuals retinal vessels were attenuated and in two subjects peripheral areas of retinal atrophy were present. An absent or severely reduced PERG was detected in all subjects, indicative of marked macular dysfunction. Full field ERG showed abnormal rod and cone responses. AF imaging revealed decreased macular AF centrally surrounded by a ring of increased AF in the majority of individuals. “ Bull’ s eye” lesions were present in two individuals, comprising of a ring of decreased perifoveal AF bordered peripherally and centrally by increased AF. Photopic sensitivity testing demonstrated elevated central visual field thresholds with additional superior greater than inferior peripheral field loss. There were rod and cone sensitivity reductions in the central and peripheral visual fields, with the inferior retina being more affected than the superior. Conclusions: The detailed phenotype is described of the autosomal dominant cone-red dystrophy, CORD7, which is associated with a point mutation in RIM1, a gene encoding a photoreceptor synaptic protein. The pattern of disease progression and long term visual outcome facilitates improved genetic counselling and advice on prognosis. Such phenotypic data will be invaluable in the event of future therapy.
文摘Aims: To characterise the detailed phenotype of “cone dystrophy with supernor mal rod ERG”in a case series of 10 patients. Methods: 10 affected patients were examined clinically and underwent colour fundus photography, with nine undergoi ng detailed electrophysiological testing. Five patients were assessed further wi th fundus autofluorescence (AF)imaging, automated photopic and dark adapted peri metry, and dark adaptometry. Detailed colour vision assessment was performed in six subjects. Blood samples were taken from four patients for DNA extraction and mutation screening of NR2E3was undertaken. Results: The onset of symptoms was i n the first and second decades of life. Subjects presented with reduced central vision and marked photophobia. All individuals were myopic and colour vision tes ting revealed severely reduced colour discrimination predominantly along the red -green axes; tritan colour vision was relatively well preserved. Nyctalopia is a later feature of the disorder. Funduscopy and AF imaging revealed a range of m acular appearances. There was electrophysiological evidence of marked macular dy sfunction, reduced and delayed cone responses, and supernormal and delayed rod r esponses. Photopic and dark adapted perimetry revealed central scotomata with wi despread peripheral sensitivity loss. No disease causing sequence variants in NR 2E3 were identified. Conclusions: The largest case series to date has been descr ibed of the clinical, psychophysical and electrophysiological characteristics of this unusual cone dystrophy with supernormal rod responses. Electrophysiologica l data were consistent with a post-phototransduction, but pre-inner nuclear la yer, site of dysfunction. While the definitive diagnosis can only be made with e lectrophysiological testing, several characteristics that may increase suspicion of this diagnosis are presented.
