ATP1A3 mutation as a candidate cause of autosomal dominant cone-rod dystrophy

Zhou, Gao-Hui; Ma, Yue; Li, Menglan; Zhou, Xinyi; Mou, Hao; Jin, Zi‐Bing

doi:10.1007/s00439-020-02182-y

Cited by 6 publications

(9 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Whole-exome sequencing was performed as previously described with the Exome Enrichment V5 Kit (Agilent Technologies, United States) (Jin et al, 2018;Cai et al, 2019b;Zhou et al, 2020). DNA fragments were sequenced on Illumina HiSeq 2000 Analyzers (90 cycles per read).…”

Section: Whole-exome Sequencingmentioning

confidence: 99%

Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China

Liu

Zhang

Piao

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

High myopia (HM) is one of the leading causes of visual impairment worldwide. In order to expand the myopia gene spectrum in the Chinese population, we investigated genetic mutations in a cohort of 27 families with HM from Northwest China by using whole-exome sequencing (WES). Genetic variations were filtered using bioinformatics tools and cosegregation analysis. A total of 201 candidate mutations were detected, and 139 were cosegregated with the disease in the families. Multistep analysis revealed four missense variants in four unrelated families, including c.904C>T (p.R302C) in CSMD1, c.860G>A (p.R287H) in PARP8, c.G848A (p.G283D) in ADAMTSL1, and c.686A>G (p.H229R) in FNDC3B. These mutations were rare or absent in the Exome Aggregation Consortium (ExAC), 1000 Genomes Project, and Genome Aggregation Database (gnomAD), indicating that they are new candidate disease-causing genes. Our findings not only expand the myopia gene spectrum but also provide reference information for further genetic study of heritable HM.

show abstract

Section: Whole-exome Sequencingmentioning

confidence: 99%

Whole-Exome Sequencing in a Cohort of High Myopia Patients in Northwest China

Liu

Zhang

Piao

et al. 2021

Front. Cell Dev. Biol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ROSA26- ATP1A3 D591V mouse model [ Gt(ROSA)26Sor tm1(CAG- ATP1A3 -D591V,-EGFP) ], carrying the mutation D591V in ATP1A3 identified in adCORD, was generated via homologous recombination in C57BL/6-derived ES cells ( Zhou et al, 2020 ). However, the endogenous mouse Atp1a3 gene was left intact.…”

Section: Animal Models Of Atp1a3 -Related Neurological Disordersmentioning

confidence: 99%

“…However, the endogenous mouse Atp1a3 gene was left intact. Instead, a human ATP1A3 cDNA harbouring D591V, under the control of the CMV early enhancer/chicken β-actin (CAG) promoter, was introduced into the mouse Gt(ROSA)26Sor locus ( Zhou et al, 2020 ), which is a widely used site for the integration of transgenes. The CAG promotor drives strong and ubiquitous gene expression, in contrast to the Atp1a3 promoter that drives selective expression in neurones.…”

Section: Animal Models Of Atp1a3 -Related Neurological Disordersmentioning

confidence: 99%

“…Heterozygous ROSA26 -ATP1A3 D591V/+ mice with a C57BL/6 genetic background had unaltered electroretinogram (ERG) responses and retinal cell morphology at 3 months of age (young adult), but maximal ERG responses were decreased at 12 months, indicative of cone and rod dysfunction ( Zhou et al, 2020 ). ROSA26 -ATP1A3 D591V/+ mice thus had a comparatively later onset and less severe retinal dysfunction than that exhibited by D591V heterozygous adCORD patients ( Zhou et al, 2020 ). This could be because, unlike D591V/+ heterozygous adCORD patients, both copies of the NKA α3 gene are intact in ROSA26 -ATP1A3 D591V/+ mice.…”

Section: Animal Models Of Atp1a3 -Related Neurological Disordersmentioning

confidence: 99%

“…Affected individuals typically present with progressive loss of vision, reduced visual acuity and problems with colour vision from the age of 12 ( Thiadens et al, 2012 ). The ATP1A3 mutation D591V has been identified in a single family affected by a form of adCORD ( Zhou et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Genetically altered animal models forATP1A3-related disorders

Ogbeta

Clapcote

2021

Disease Models &Amp; Mechanisms

View full text Add to dashboard Cite

Within the past 20 years, particularly with the advent of exome sequencing technologies, autosomal dominant and de novo mutations in the gene encoding the neurone-specific α3 subunit of the Na+,K+-ATPase (NKA α3) pump, ATP1A3, have been identified as the cause of a phenotypic continuum of rare neurological disorders. These allelic disorders of ATP1A3 include (in approximate order of severity/disability and onset in childhood development): polymicrogyria; alternating hemiplegia of childhood; cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing loss syndrome; relapsing encephalopathy with cerebellar ataxia; and rapid-onset dystonia-parkinsonism. Some patients present intermediate, atypical or combined phenotypes. As these disorders are currently difficult to treat, there is an unmet need for more effective therapies. The molecular mechanisms through which mutations in ATP1A3 result in a broad range of neurological symptoms are poorly understood. However, in vivo comparative studies using genetically altered model organisms can provide insight into the biological consequences of the disease-causing mutations in NKA α3. Herein, we review the existing mouse, zebrafish, Drosophila and Caenorhabditis elegans models used to study ATP1A3-related disorders, and discuss their potential contribution towards the understanding of disease mechanisms and development of novel therapeutics.

show abstract