Your browser doesn't support javascript.
loading
ATP1A3 mutation as a candidate cause of autosomal dominant cone-rod dystrophy.
Zhou, Gao-Hui; Ma, Yue; Li, Meng-Lan; Zhou, Xin-Yi; Mou, Hao; Jin, Zi-Bing.
Afiliação
  • Zhou GH; Lab for Stem Cell and Retinal Regeneration, Division of Ophthalmic Genetics, The Eye Hospital, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou Medical University, Wenzhou, 325027, China.
  • Ma Y; Lab for Stem Cell and Retinal Regeneration, Division of Ophthalmic Genetics, The Eye Hospital, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou Medical University, Wenzhou, 325027, China.
  • Li ML; Lab for Stem Cell and Retinal Regeneration, Division of Ophthalmic Genetics, The Eye Hospital, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou Medical University, Wenzhou, 325027, China.
  • Zhou XY; Lab for Stem Cell and Retinal Regeneration, Division of Ophthalmic Genetics, The Eye Hospital, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou Medical University, Wenzhou, 325027, China.
  • Mou H; Lab for Stem Cell and Retinal Regeneration, Division of Ophthalmic Genetics, The Eye Hospital, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou Medical University, Wenzhou, 325027, China.
  • Jin ZB; Lab for Stem Cell and Retinal Regeneration, Division of Ophthalmic Genetics, The Eye Hospital, National Center for International Research in Regenerative Medicine and Neurogenetics, Wenzhou Medical University, Wenzhou, 325027, China. jinzb@mail.eye.ac.cn.
Hum Genet ; 139(11): 1391-1401, 2020 Nov.
Article em En | MEDLINE | ID: mdl-32440726
ABSTRACT
Cone-rod dystrophy (CORD) is an inherited retinal degenerative disease characterized by progressive loss of cone and rod photoreceptors. Although several genes have been reported to cause autosomal dominant CORD (adCORD), the genetic causes of adCORD have not been fully elucidated. Here, we identified the ATP1A3 gene, encoding the α3 subunit of Na+, K+-ATPase, as a novel gene associated with adCORD. Using whole-exome sequencing (WES), we found a candidate mutation of ATP1A3 that co-segregated with the disease in an analysis of two affected patients and one healthy relative in an adCORD family. According to our RNA-seq data, we demonstrated that the Atp1a3 mRNA level was extremely high in the murine retina. Overexpression of mutant ATP1A3 in vitro led to a reduced oxygen consumption rate (OCR), reflecting the limited mitochondrial reserve capacity. Furthermore, we generated transgenic mice expressing the ATP1A3 cDNA with patient variant and found decreased electroretinogram (ERG) responses. Moreover, the mutant ATP1A3 is highly expressed in photoreceptor inner segment, where mitochondria are enriched. These results suggest that the ATP1A3 mutation is a new genetic cause responsible for adCORD and indicate that ATP1A3 plays an important role in retinal function.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: ATPase Trocadora de Sódio-Potássio / Distrofias de Cones e Bastonetes / Genes Dominantes / Mutação Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: ATPase Trocadora de Sódio-Potássio / Distrofias de Cones e Bastonetes / Genes Dominantes / Mutação Idioma: En Ano de publicação: 2020 Tipo de documento: Article