R Mukherjee1, A G Robson1, G E Holder1, A Stockman2, C A Egan1, A T Moore1, A R Webster1. 1. 1] Moorfields Eye Hospital NHS Foundation Trust, London, UK [2] Institute of Ophthalmology, University College London London, UK. 2. Institute of Ophthalmology, University College London London, UK.
Abstract
PURPOSE: The purpose of this study is to describe the phenotype of a family with de novo mutation in the GUCY2D. MATERIALS AND METHODS: Five subjects, including two monozygotic twins, underwent ophthalmic clinical examination while some had autofluorescence imaging (AF) and optical coherence tomography (OCT). Symptomatic individuals underwent electrophysiological testing. The youngest subject (21 years) was also evaluated psychophysically. DNA obtained from the individuals was screened for mutations in GUCY2D. Microsatellite markers were used to determine the haplotype of 17p surrounding the GUCY2D gene. RESULTS: The youngest subject had 6/18 visual acuity, an annulus of hyper-autofluorescence in the perifoveal region, and a subfoveal absence of outer segments on OCT. In the older individuals, severe thinning of inner retina and a patchy loss of photoreceptors and retinal pigment epithelium were observed in the perifoveal region. All three showed generalised cone system dysfunction with preserved rod function on electrophysiology. Psychophysical evaluation was consistent with poor cone function. Screening of the GUCY2D gene revealed the mutation p.R838H in all the affected individuals and was absent in the asymptomatic patients. Haplotyping showed that the mutation originated from the unaffected mother. CONCLUSIONS: Autosomal dominant cone dystrophy due to GUCY2D can occur without a history in the antecedents due to a de novo mutation. This is important to consider in any simplex case with a similar phenotype. The phenotype description of this disorder is expanded with detailed description of the OCT findings. This paper describes the concordance of the phenotypic findings in the monozygotic twins.
PURPOSE: The purpose of this study is to describe the phenotype of a family with de novo mutation in the GUCY2D. MATERIALS AND METHODS: Five subjects, including two monozygotic twins, underwent ophthalmic clinical examination while some had autofluorescence imaging (AF) and optical coherence tomography (OCT). Symptomatic individuals underwent electrophysiological testing. The youngest subject (21 years) was also evaluated psychophysically. DNA obtained from the individuals was screened for mutations in GUCY2D. Microsatellite markers were used to determine the haplotype of 17p surrounding the GUCY2D gene. RESULTS: The youngest subject had 6/18 visual acuity, an annulus of hyper-autofluorescence in the perifoveal region, and a subfoveal absence of outer segments on OCT. In the older individuals, severe thinning of inner retina and a patchy loss of photoreceptors and retinal pigment epithelium were observed in the perifoveal region. All three showed generalised cone system dysfunction with preserved rod function on electrophysiology. Psychophysical evaluation was consistent with poor cone function. Screening of the GUCY2D gene revealed the mutation p.R838H in all the affected individuals and was absent in the asymptomatic patients. Haplotyping showed that the mutation originated from the unaffected mother. CONCLUSIONS:Autosomal dominant cone dystrophy due to GUCY2D can occur without a history in the antecedents due to a de novo mutation. This is important to consider in any simplex case with a similar phenotype. The phenotype description of this disorder is expanded with detailed description of the OCT findings. This paper describes the concordance of the phenotypic findings in the monozygotic twins.
Authors: Andrew Stockman; Hannah E Smithson; Andrew R Webster; Graham E Holder; Naheed A Rana; Caterina Ripamonti; Lindsay T Sharpe Journal: J Vis Date: 2008-01-17 Impact factor: 2.240
Authors: S E Wilkie; R J Newbold; E Deery; C E Walker; I Stinton; V Ramamurthy; J B Hurley; S S Bhattacharya; M J Warren; D M Hunt Journal: Hum Mol Genet Date: 2000-12-12 Impact factor: 6.150
Authors: X Liu; K Seno; Y Nishizawa; F Hayashi; A Yamazaki; H Matsumoto; T Wakabayashi; J Usukura Journal: Exp Eye Res Date: 1994-12 Impact factor: 3.467
Authors: Alberta A H J Thiadens; Anneke I den Hollander; Susanne Roosing; Sander B Nabuurs; Renate C Zekveld-Vroon; Rob W J Collin; Elfride De Baere; Robert K Koenekoop; Mary J van Schooneveld; Tim M Strom; Janneke J C van Lith-Verhoeven; Andrew J Lotery; Norka van Moll-Ramirez; Bart P Leroy; L Ingeborgh van den Born; Carel B Hoyng; Frans P M Cremers; Caroline C W Klaver Journal: Am J Hum Genet Date: 2009-07-16 Impact factor: 11.025
Authors: K Tyler McCullough; Sanford L Boye; Diego Fajardo; Kaitlyn Calabro; James J Peterson; Christianne E Strang; Dibyendu Chakraborty; Sebastian Gloskowski; Scott Haskett; Steven Samuelsson; Haiyan Jiang; C Douglas Witherspoon; Paul D Gamlin; Morgan L Maeder; Shannon E Boye Journal: Hum Gene Ther Date: 2018-12-20 Impact factor: 5.695
Authors: Jonas Neubauer; Leo Hahn; Johannes Birtel; Camiel J F Boon; Peter Charbel Issa; M Dominik Fischer Journal: Genes (Basel) Date: 2022-02-08 Impact factor: 4.096