Identification and Analysis of Inherited Retinal Disease Genes

Neveling, Kornelia; Hollander, Anneke I. den; Cremers, Frans P.M.; Collin, Rob W.J.

doi:10.1007/978-1-62703-080-9_1

Cited by 17 publications

(17 citation statements)

References 69 publications

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Section: Introductionmentioning

confidence: 99%

“…RP is primarily associated with the rod photoreceptors, while the cone cells are compromised as the disease progresses [3]. RP individuals exhibit degeneration of photoreceptors or the retinal pigment epithelium (RPE) of the retina in the initial stages of the disease, followed by a progressive reduction in the visual field and visual loss [3]. Other ocular findings include atrophic changes in the photoreceptors and RPE followed by the appearing of melanin-containing structures in the retinal vascular layer [3].…”

Section: Introductionmentioning

confidence: 99%

“…RP individuals exhibit degeneration of photoreceptors or the retinal pigment epithelium (RPE) of the retina in the initial stages of the disease, followed by a progressive reduction in the visual field and visual loss [3]. Other ocular findings include atrophic changes in the photoreceptors and RPE followed by the appearing of melanin-containing structures in the retinal vascular layer [3]. The fundus changes include a pale optic nerve, attenuated retinal vessels, and bone spicule-like pigmentation in the mid-peripheral retina [3].…”

Section: Introductionmentioning

confidence: 99%

“…Other ocular findings include atrophic changes in the photoreceptors and RPE followed by the appearing of melanin-containing structures in the retinal vascular layer [3]. The fundus changes include a pale optic nerve, attenuated retinal vessels, and bone spicule-like pigmentation in the mid-peripheral retina [3]. …”

Section: Introductionmentioning

confidence: 99%

“…The clinical distinction between the subtypes of RP, however, is not always clear and there are largely overlapped in phenotype between RP, LCA (Leber's congenital amaurosis), COD or CORD (cone or cone-rod dystrophy) and other retinal diseases [3]. Also, there are other non-RP diseases caused by mutations in the same genes involved with RP.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Targeted next generation sequencing identified novel mutations in RPGRIP1 associated with both retinitis pigmentosa and Leber’s congenital amaurosis in unrelated Chinese patients

et al. 2017

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As the most common inherited retinal degenerations, retinitis pigmentosa (RP) is clinically and genetically heterogeneous. Some of the RP genes are also associated with other retinal diseases, such as LCA (Leber's congenital amaurosis) and CORD (cone-rod dystrophy). Here, in our molecular diagnosis of 99 Chinese RP patients using targeted gene capture sequencing, three probands were found to carry mutations of RPGRIP1, which was known to be associated with pathogenesis of LCA and CORD. By further clinical analysis, two probands were confirmed to be RP patients and one was confirmed to be LCA patient. These novel mutations were co-segregated with the disease phenotype in their families. Our result not only expands the mutational spectrum of the RPGRIP1 gene but also gives supports to clinical diagnosis and molecular treatment of RP patients.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Targeted next generation sequencing identified novel mutations in RPGRIP1 associated with both retinitis pigmentosa and Leber’s congenital amaurosis in unrelated Chinese patients

et al. 2017

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Mutations in RARS cause hypomyelination

Wolf

Salomons

Rodenburg

et al. 2014

Annals of Neurology

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Hypomyelinating disorders of the central nervous system are still a diagnostic challenge, as many patients remain without genetic diagnosis. Using magnetic resonance imaging (MRI) pattern recognition and whole exome sequencing, we could ascertain compound heterozygous mutations in RARS in 4 patients with hypomyelination. Clinical features included severe spasticity and nystagmus. RARS encodes the cytoplasmic arginyl-tRNA synthetase, an enzyme essential for RNA translation. This protein is among the subunits of the multisynthetase complex, which emerges as a key player in myelination.

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Hidden Genetic Variation in LCA9‐Associated Congenital Blindness Explained by 5′UTR Mutations and Copy‐Number Variations of NMNAT1

et al. 2015

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Leber congenital amaurosis (LCA) is a severe autosomal‐recessive retinal dystrophy leading to congenital blindness. A recently identified LCA gene is NMNAT1, located in the LCA9 locus. Although most mutations in blindness genes are coding variations, there is accumulating evidence for hidden noncoding defects or structural variations (SVs). The starting point of this study was an LCA9‐associated consanguineous family in which no coding mutations were found in the LCA9 region. Exploring the untranslated regions of NMNAT1 revealed a novel homozygous 5′UTR variant, c.‐70A>T. Moreover, an adjacent 5′UTR variant, c.‐69C>T, was identified in a second consanguineous family displaying a similar phenotype. Both 5′UTR variants resulted in decreased NMNAT1 mRNA abundance in patients’ lymphocytes, and caused decreased luciferase activity in human retinal pigment epithelial RPE‐1 cells. Second, we unraveled pseudohomozygosity of a coding NMNAT1 mutation in two unrelated LCA patients by the identification of two distinct heterozygous partial NMNAT1 deletions. Molecular characterization of the breakpoint junctions revealed a complex Alu‐rich genomic architecture. Our study uncovered hidden genetic variation in NMNAT1‐associated LCA and emphasized a shift from coding to noncoding regulatory mutations and repeat‐mediated SVs in the molecular pathogenesis of heterogeneous recessive disorders such as hereditary blindness.

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Identification and Analysis of Inherited Retinal Disease Genes

Cited by 17 publications

References 69 publications

Targeted next generation sequencing identified novel mutations in RPGRIP1 associated with both retinitis pigmentosa and Leber’s congenital amaurosis in unrelated Chinese patients

Targeted next generation sequencing identified novel mutations in RPGRIP1 associated with both retinitis pigmentosa and Leber’s congenital amaurosis in unrelated Chinese patients

Mutations in RARS cause hypomyelination

Hidden Genetic Variation in LCA9‐Associated Congenital Blindness Explained by 5′UTR Mutations and Copy‐Number Variations of NMNAT1

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