Jian Liang1,2, Xiangjun She1, Jieqiong Chen1, Yuanqi Zhai1,3, Yang Liu1, Kairong Zheng1, Yuanyuan Gong1, Hong Zhu1,3, Xueting Luo4,5,6, Xiaodong Sun1,2,3. 1. Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. 2. Shanghai Key Laboratory of Fundus Diseases, 100 Haining Road, Shanghai, 200080, China. 3. Shanghai Engineering Center for Visual Science and Photomedicine, 100 Haining Road, Shanghai, 200080, China. 4. Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai, 200080, China. xtluo@sjtu.edu.cn. 5. Shanghai Key Laboratory of Fundus Diseases, 100 Haining Road, Shanghai, 200080, China. xtluo@sjtu.edu.cn. 6. Shanghai Engineering Center for Visual Science and Photomedicine, 100 Haining Road, Shanghai, 200080, China. xtluo@sjtu.edu.cn.
Abstract
PURPOSE: To characterize two patients with macular and rod-cone dystrophy and identify the genetic basis for disease. METHOD: Ophthalmic examinations were performed for the family and the peripheral blood samples were collected for whole exome sequencing. The mutated sequences of PROM1 gene were cloned and expressed in cultured cell lines after transient transfection followed by analysis with confocal microscopy and bridge-PCR. RESULT: We reported that two patients, brothers in a family, were diagnosed with macular and rod-cone dystrophy. Phenotypically, both patients experience progressive visual impairment and nyctalopia. The fundus examination showed macular and choroid dystrophy with pigment deposits in the macular region. Functionally, photoreceptor response to electrophysiological stimulation was significantly compromised with more severe decline in rods. Genetic analysis by whole exome sequencing revealed two novel compound heterogeneous point mutations in PROM1 gene that co-segregate with patients in an autosomal recessive manner. Specifically, the c.C1902G(p.Y634X) nonsense mutation results in a truncated, labile, and mislocalized protein, while the c.C1682+3A>G intronic mutation disrupts messenger RNA splicing. CONCLUSION: Our findings have identified two novel deleterious mutations in PROM1 gene that are associated with hereditary macular and rod-cone dystrophy in human.
PURPOSE: To characterize two patients with macular and rod-cone dystrophy and identify the genetic basis for disease. METHOD: Ophthalmic examinations were performed for the family and the peripheral blood samples were collected for whole exome sequencing. The mutated sequences of PROM1 gene were cloned and expressed in cultured cell lines after transient transfection followed by analysis with confocal microscopy and bridge-PCR. RESULT: We reported that two patients, brothers in a family, were diagnosed with macular and rod-cone dystrophy. Phenotypically, both patients experience progressive visual impairment and nyctalopia. The fundus examination showed macular and choroid dystrophy with pigment deposits in the macular region. Functionally, photoreceptor response to electrophysiological stimulation was significantly compromised with more severe decline in rods. Genetic analysis by whole exome sequencing revealed two novel compound heterogeneous point mutations in PROM1 gene that co-segregate with patients in an autosomal recessive manner. Specifically, the c.C1902G(p.Y634X) nonsense mutation results in a truncated, labile, and mislocalized protein, while the c.C1682+3A>G intronic mutation disrupts messenger RNA splicing. CONCLUSION: Our findings have identified two novel deleterious mutations in PROM1 gene that are associated with hereditary macular and rod-cone dystrophy in human.
Entities:
Keywords:
Hereditary retinal disease; Macular and rod-cone dystrophy; PROM1
Authors: Jasmina Cehajic-Kapetanovic; Johannes Birtel; Michelle E McClements; Morag E Shanks; Penny Clouston; Susan M Downes; Peter Charbel Issa; Robert E MacLaren Journal: JAMA Netw Open Date: 2019-06-05
Authors: Sara D Ragi; Jose Ronaldo Lima de Carvalho; Akemi J Tanaka; Karen Sophia Park; Vinit B Mahajan; Irene H Maumenee; Stephen H Tsang Journal: Cold Spring Harb Mol Case Stud Date: 2019-12-13