PURPOSE: To provide an up to 14-year overview of the early ocular phenotype in siblings with a homozygous p.G461R mutation in the KCNV2 gene. METHODS: Two brothers and their sister were followed-up clinically from ages 5 years, 4 years, and 2 months, respectively, including complete ophthalmological examinations. Goldmann visual fields, two-color-threshold (2CT) perimetry, color vision testing, optical coherence tomography (OCT), fundus autofluorescence (FAF), and Ganzfeld electroretinograms (ERGs) were performed according to age-related capabilities. Genetic analyses included whole genome linkage analysis, homozygosity mapping, and candidate gene sequencing. RESULTS: All three siblings were homozygous for the p.G461R mutation. At 5 months, the younger brother had no nystagmus and Teller-acuity of 3.2 cyc/deg. At older age, all three presented nystagmus, increased light sensitivity, reduced color discrimination, and relative central scotomas. Visual acuities ranged from 20/200 to 20/70. The macula developed minor irregularities of the RPE, thinning in optical coherence tomography, and a ring of increased FAF. Scotopic (rod) sensitivity was reduced by 2 log and photopic sensitivity by 1 log in two-color-threshold perimetry. ERG responses were markedly delayed. Photopic amplitudes were severely reduced. Scotopic b-waves rose steeply with flash intensity, but for the standard flash supernormal amplitudes were only reached in the girl. CONCLUSIONS: FAF was similar to that in cone-rod dystrophy. Although cone dysfunction was accompanied by rod dysfunction, and scotopic ERGs in patient 2 deteriorated, no patient demonstrated any unequivocal sign of rod degeneration. Grossly delayed b-waves with a steep response-versus-intensity relationship rather than supernormal amplitudes should remind clinicians of this specific condition.
PURPOSE: To provide an up to 14-year overview of the early ocular phenotype in siblings with a homozygous p.G461R mutation in the KCNV2 gene. METHODS: Two brothers and their sister were followed-up clinically from ages 5 years, 4 years, and 2 months, respectively, including complete ophthalmological examinations. Goldmann visual fields, two-color-threshold (2CT) perimetry, color vision testing, optical coherence tomography (OCT), fundus autofluorescence (FAF), and Ganzfeld electroretinograms (ERGs) were performed according to age-related capabilities. Genetic analyses included whole genome linkage analysis, homozygosity mapping, and candidate gene sequencing. RESULTS: All three siblings were homozygous for the p.G461R mutation. At 5 months, the younger brother had no nystagmus and Teller-acuity of 3.2 cyc/deg. At older age, all three presented nystagmus, increased light sensitivity, reduced color discrimination, and relative central scotomas. Visual acuities ranged from 20/200 to 20/70. The macula developed minor irregularities of the RPE, thinning in optical coherence tomography, and a ring of increased FAF. Scotopic (rod) sensitivity was reduced by 2 log and photopic sensitivity by 1 log in two-color-threshold perimetry. ERG responses were markedly delayed. Photopic amplitudes were severely reduced. Scotopic b-waves rose steeply with flash intensity, but for the standard flash supernormal amplitudes were only reached in the girl. CONCLUSIONS: FAF was similar to that in cone-rod dystrophy. Although cone dysfunction was accompanied by rod dysfunction, and scotopic ERGs in patient 2 deteriorated, no patient demonstrated any unequivocal sign of rod degeneration. Grossly delayed b-waves with a steep response-versus-intensity relationship rather than supernormal amplitudes should remind clinicians of this specific condition.
Authors: Frederick T Collison; Jason C Park; Gerald A Fishman; Edwin M Stone; J Jason McAnany Journal: Doc Ophthalmol Date: 2019-03-29 Impact factor: 2.379
Authors: Michalis Georgiou; Anthony G Robson; Kaoru Fujinami; Shaun M Leo; Ajoy Vincent; Fadi Nasser; Thales Antônio Cabral De Guimarães; Samer Khateb; Nikolas Pontikos; Yu Fujinami-Yokokawa; Xiao Liu; Kazushige Tsunoda; Takaaki Hayashi; Mauricio E Vargas; Alberta A H J Thiadens; Emanuel R de Carvalho; Xuan-Thanh-An Nguyen; Gavin Arno; Omar A Mahroo; Maria Inmaculada Martin-Merida; Belen Jimenez-Rolando; Gema Gordo; Ester Carreño; Ayuso Carmen; Dror Sharon; Susanne Kohl; Rachel M Huckfeldt; Bernd Wissinger; Camiel J F Boon; Eyal Banin; Mark E Pennesi; Arif O Khan; Andrew R Webster; Eberhart Zrenner; Elise Héon; Michel Michaelides Journal: Am J Ophthalmol Date: 2020-12-11 Impact factor: 5.258
Authors: Thales A C De Guimaraes; Michalis Georgiou; Anthony G Robson; Michel Michaelides Journal: Ophthalmic Genet Date: 2020-05-22 Impact factor: 1.803