Ayami Nakanishi1, Shinji Ueno2, Takaaki Hayashi3, Satoshi Katagiri3, Taro Kominami1, Yasuki Ito1, Tamaki Gekka3, Yoichiro Masuda3, Hiroshi Tsuneoka3, Kei Shinoda4, Akito Hirakata5, Makoto Inoue5, Kaoru Fujinami6, Kazushige Tsunoda6, Takeshi Iwata7, Hiroko Terasaki1. 1. Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan. 2. Department of Ophthalmology, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: ueno@med.nagoya-u.ac.jp. 3. Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan. 4. Department of Ophthalmology, Teikyo University School of Medicine, Tokyo, Japan. 5. Department of Ophthalmology, Kyorin University School of Medicine, Tokyo, Japan. 6. Laboratory of Visual Physiology, Division of Vision Research, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan. 7. Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization, Tokyo Medical Center, Tokyo, Japan.
Abstract
PURPOSE: To report the clinical and genetic findings of 9 Japanese patients with autosomal recessive bestrophinopathy (ARB). DESIGN: Retrospective, multicenter observational case series. METHODS: Nine ARB patients from 7 unrelated Japanese families that were examined in 3 institutions in Japan were studied. A series of ophthalmic examinations including fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, electrooculography (EOG), electroretinography, and the results of genetic analysis were reviewed. RESULTS: Genetic analyses identified 7 pathogenic variants in BEST1 including 2 novel variants, c.478G>C (p.A160P) and c.948+1delG. Homozygous variants were found in 4 families and compound heterozygous variants were found in 3 families. Two patients were diagnosed as ARB only after the whole exome sequencing analyses. The Arden ratio of the EOG was less than 1.5 in all 7 patients tested. Vitelliform lesions typical for Best vitelliform macular dystrophy were not seen in any of the patients. Seven patients shared some of the previously described features of ARB: subretinal deposits, extensive subretinal fluid, and cystoid macular edema (CME). However, the other 2 patients with severe retinal degeneration lacked these features. Focal choroidal excavations were present bilaterally in 2 patients. One case had a marked reduction of the CME and expansion of subretinal deposits over an 8-year of follow-up period. CONCLUSIONS: Japanese ARB patients had some but not all of the previously described features. Genetic analyses are essential to diagnose ARB correctly in consequence of considerable phenotypic variations.
PURPOSE: To report the clinical and genetic findings of 9 Japanese patients with autosomal recessive bestrophinopathy (ARB). DESIGN: Retrospective, multicenter observational case series. METHODS: Nine ARBpatients from 7 unrelated Japanese families that were examined in 3 institutions in Japan were studied. A series of ophthalmic examinations including fundus photography, spectral-domain optical coherence tomography, fundus autofluorescence, electrooculography (EOG), electroretinography, and the results of genetic analysis were reviewed. RESULTS: Genetic analyses identified 7 pathogenic variants in BEST1 including 2 novel variants, c.478G>C (p.A160P) and c.948+1delG. Homozygous variants were found in 4 families and compound heterozygous variants were found in 3 families. Two patients were diagnosed as ARB only after the whole exome sequencing analyses. The Arden ratio of the EOG was less than 1.5 in all 7 patients tested. Vitelliform lesions typical for Best vitelliform macular dystrophy were not seen in any of the patients. Seven patients shared some of the previously described features of ARB: subretinal deposits, extensive subretinal fluid, and cystoid macular edema (CME). However, the other 2 patients with severe retinal degeneration lacked these features. Focal choroidal excavations were present bilaterally in 2 patients. One case had a marked reduction of the CME and expansion of subretinal deposits over an 8-year of follow-up period. CONCLUSIONS: Japanese ARBpatients had some but not all of the previously described features. Genetic analyses are essential to diagnose ARB correctly in consequence of considerable phenotypic variations.
Authors: Imen Habibi; Yosra Falfoul; Margarita G Todorova; Stefan Wyrsch; Veronika Vaclavik; Maria Helfenstein; Ahmed Turki; Khaled El Matri; Leila El Matri; Daniel F Schorderet Journal: Genes (Basel) Date: 2019-11-21 Impact factor: 4.096
Authors: Karsten Hufendiek; Katerina Hufendiek; Herbert Jägle; Heidi Stöhr; Marius Book; Georg Spital; Günay Rustambayova; Carsten Framme; Bernhard H F Weber; Agnes B Renner; Ulrich Kellner Journal: Int J Mol Sci Date: 2020-12-08 Impact factor: 5.923