Takaaki Hayashi1,2, Katsuhiro Hosono3, Kentaro Kurata3, Satoshi Katagiri4, Kei Mizobuchi4, Shinji Ueno5, Mineo Kondo6, Tadashi Nakano4, Yoshihiro Hotta3. 1. Department of Ophthalmology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan. taka@jikei.ac.jp. 2. Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, 6-41-2 Aoto, Katsushika-ku, Tokyo, 125-8506, Japan. taka@jikei.ac.jp. 3. Department of Ophthalmology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan. 4. Department of Ophthalmology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan. 5. Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. 6. Department of Ophthalmology, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
Abstract
PURPOSE: A single variant (p.G38D) in the GNAT1 gene, encoding the rod-specific transducin α-subunit in phototransduction, has been reported only in one French family with Nougaret-type autosomal dominant congenital stationary night blindness (CSNB). We identified a Japanese family with Nougaret-type CSNB and cone-rod dystrophy (CORD). METHODS: Five patients with CSNB and two patients with childhood-onset CORD were recruited. We performed a comprehensive ophthalmic examination including electroretinography (ERG). Disease-causing variants were identified by whole exome sequencing, with candidates confirmed by Sanger sequencing in nine family members. RESULTS: The GNAT1 variant (p.G38D) was identified in all four CSNB patients, whereas the two CORD patients carried biallelic truncated known ABCA4 variants as well as the GNAT1 variant. Clinically, no remarkable findings were observed in fuduscopy, fundus autofluorescence, or optical coherence tomography images from the CSNB patients. No response was detectable by rod ERG. The a-waves of standard and bright flash ERG were delayed and broadened rather than biphasic, and b/a-wave amplitude ratio was negative. Cone and 30-Hz flicker responses were normal, and overall, the ERG findings were compatible with previous descriptions of Nougaret-type CSNB. ERG of the CORD patients with macular atrophy showed non-recordable rod response and severely decreased standard flash, cone and 30-Hz flicker responses. CONCLUSIONS: This is the second report of a Nougaret-type CSNB family with the GNAT1 variant. Our novel findings suggest that coexistence of the GNAT1 and biallelic ABCA4 variants is associated with an overlapping phenotype with both Nougaret-type CSNB and CORD.
PURPOSE: A single variant (p.G38D) in the GNAT1 gene, encoding the rod-specific transducin α-subunit in phototransduction, has been reported only in one French family with Nougaret-type autosomal dominant congenital stationary night blindness (CSNB). We identified a Japanese family with Nougaret-type CSNB and cone-rod dystrophy (CORD). METHODS: Five patients with CSNB and two patients with childhood-onset CORD were recruited. We performed a comprehensive ophthalmic examination including electroretinography (ERG). Disease-causing variants were identified by whole exome sequencing, with candidates confirmed by Sanger sequencing in nine family members. RESULTS: The GNAT1 variant (p.G38D) was identified in all four CSNB patients, whereas the two CORD patients carried biallelic truncated known ABCA4 variants as well as the GNAT1 variant. Clinically, no remarkable findings were observed in fuduscopy, fundus autofluorescence, or optical coherence tomography images from the CSNB patients. No response was detectable by rod ERG. The a-waves of standard and bright flash ERG were delayed and broadened rather than biphasic, and b/a-wave amplitude ratio was negative. Cone and 30-Hz flicker responses were normal, and overall, the ERG findings were compatible with previous descriptions of Nougaret-type CSNB. ERG of the CORD patients with macular atrophy showed non-recordable rod response and severely decreased standard flash, cone and 30-Hz flicker responses. CONCLUSIONS: This is the second report of a Nougaret-type CSNB family with the GNAT1 variant. Our novel findings suggest that coexistence of the GNAT1 and biallelic ABCA4 variants is associated with an overlapping phenotype with both Nougaret-type CSNB and CORD.
Authors: Mustapha Moussaif; William W Rubin; Vasily Kerov; Rebecca Reh; Desheng Chen; Janis Lem; Ching-Kang Chen; James B Hurley; Marie E Burns; Nikolai O Artemyev Journal: J Neurosci Date: 2006-06-21 Impact factor: 6.167
Authors: Daphne L McCulloch; Michael F Marmor; Mitchell G Brigell; Ruth Hamilton; Graham E Holder; Radouil Tzekov; Michael Bach Journal: Doc Ophthalmol Date: 2014-12-14 Impact factor: 2.379
Authors: Jennifer E Posey; Tamar Harel; Pengfei Liu; Jill A Rosenfeld; Regis A James; Zeynep H Coban Akdemir; Magdalena Walkiewicz; Weimin Bi; Rui Xiao; Yan Ding; Fan Xia; Arthur L Beaudet; Donna M Muzny; Richard A Gibbs; Eric Boerwinkle; Christine M Eng; V Reid Sutton; Chad A Shaw; Sharon E Plon; Yaping Yang; James R Lupski Journal: N Engl J Med Date: 2016-12-07 Impact factor: 91.245