EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa

El-Aziz, Mai M. Abd; Barragán, Isabel; O'Driscoll, C.; Goodstadt, Leo; Prigmore, Elena; Borrego, Salud; Mena, Marcela; Pieras, Juan Ignacio; El-Ashry, Mohamed F.; Safieh, Leen Abu; Shah, Ameet; Cheetham, Michael E.; Carter, Nigel P.; Chakarova, Christina; Ponting, Chris P.; Bhattacharya, Shom Shanker; Antiñolo, Guillermo

doi:10.1038/ng.241

Cited by 174 publications

(196 citation statements)

References 13 publications

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“…1-3 CRD can manifest under a variety of inheritance models, though the autosomal recessive mode of inheritance is the most prevalent. To date, eight genes responsible for autosomal recessive CRD have been identified: ABCA4 (OMIM#601691), 4 ADAM9 (OMIM#602713), 5 C8orf37 (OMIM#614477), 6 CERKL (OMIM#608381), 7 EYS (OMIM#612424), 8 RPGRIP1 (OMIM#605446), 9 RAB28 (OMIM#612994) 10 and TULP1 (OMIM#602280). 11 However, the known variants do not account for all cases of CRD.…”

Section: Introductionmentioning

confidence: 99%

Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy

et al. 2014

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We assessed a large consanguineous Pakistani family (PKAB157) segregating early onset low vision problems. Funduscopic and electroretinographic evaluation of affected individuals revealed juvenile cone-rod dystrophy (CRD) with maculopathy. Other clinical symptoms included loss of color discrimination, photophobia and nystagmus. Whole-exome sequencing, segregation and haplotype analyses demonstrated that a transition variant (c.955T4C; p.(Cys319Arg)) in CNGA3 co-segregated with the CRD phenotype in family PKAB157. The ability of CNGA3 channel to influx calcium in response to agonist, when expressed either alone or together with the wild-type CNGB3 subunit in HEK293 cells, was completely abolished due to p.Cys319Arg variant. Western blotting and immunolocalization studies suggest that a decreased channel density in the HEK293 cell membrane due to impaired folding and/or trafficking of the CNGA3 protein is the main pathogenic effect of the p.Cys319Arg variant. Mutant alleles of the human cone photoreceptor cyclic nucleotide-gated channel (CNGA3) are frequently associated with achromatopsia. In rare cases, variants in CNGA3 are also associated with cone dystrophy, Leber's congenital amaurosis and oligo cone trichromacy. The identification of predicted p.(Cys319Arg) missense variant in CNGA3 expands the repertoire of the known genetic causes of CRD and phenotypic spectrum of CNGA3 alleles.

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Section: Introductionmentioning

confidence: 99%

Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy

et al. 2014

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“…In Table 1 we list the 44 currently known genes underlying nonsyndromic recessive retinal dystrophies in human. Mouse orthologs are known for each of these genes, except eyes shut homolog (EYS) (19). Naturally occurring or man-made…”

Section: Animal Models For Recessive Retinal Dystrophiesmentioning

confidence: 99%

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

Hollander

Black²,

Bennett³

et al. 2010

J. Clin. Invest.

183

100

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Nonsyndromic recessive retinal dystrophies cause severe visual impairment due to the death of photoreceptor and retinal pigment epithelium cells. These diseases until recently have been considered to be incurable. Molecular genetic studies in the last two decades have revealed the underlying molecular causes in approximately two-thirds of patients. The mammalian eye has been at the forefront of therapeutic trials based on gene augmentation in humans with an early-onset nonsyndromic recessive retinal dystrophy due to mutations in the retinal pigment epithelium-specific protein 65kDa (RPE65) gene. Tremendous challenges still lie ahead to extrapolate these studies to other retinal disease-causing genes, as human gene augmentation studies require testing in animal models for each individual gene and sufficiently large patient cohorts for clinical trials remain to be identified through cost-effective mutation screening protocols.

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“…23,37,38 Truncating variants within the EYS gene (OMIM 612424) were initially associated with arRP in 2008. 39,40 Novel truncating variants were identified in a patient with a clinical diagnosis of autosomal-recessive CRD. 41 Parental testing confirmed that these variants were in trans.…”

Section: Advantages Of Mps Testing Expanding Clinical Phenotypesmentioning

confidence: 99%

Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies

Lee

Garg

2015

Genetics in Medicine

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EYS, encoding an ortholog of Drosophila spacemaker, is mutated in autosomal recessive retinitis pigmentosa

Cited by 174 publications

References 13 publications

Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy

Homozygous missense variant in the human CNGA3 channel causes cone-rod dystrophy

Lighting a candle in the dark: advances in genetics and gene therapy of recessive retinal dystrophies

Navigating the current landscape of clinical genetic testing for inherited retinal dystrophies

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